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Ambrosi, C. Acinetobacter baumannii. Encyclopedia. Available online: https://encyclopedia.pub/entry/9019 (accessed on 25 April 2024).
Ambrosi C. Acinetobacter baumannii. Encyclopedia. Available at: https://encyclopedia.pub/entry/9019. Accessed April 25, 2024.
Ambrosi, Cecilia. "Acinetobacter baumannii" Encyclopedia, https://encyclopedia.pub/entry/9019 (accessed April 25, 2024).
Ambrosi, C. (2021, April 26). Acinetobacter baumannii. In Encyclopedia. https://encyclopedia.pub/entry/9019
Ambrosi, Cecilia. "Acinetobacter baumannii." Encyclopedia. Web. 26 April, 2021.
Acinetobacter baumannii
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This entry is adapted from the peer-reviewed paper 10.3390/pathogens10040387

Acinetobacter baumannii is regarded as a life-threatening pathogen associated with community-acquired and nosocomial infections, mainly pneumonia.

Acinetobacter baumannii community-acquired infections nosocomial infections

1. Introduction

The studies on Acinetobacter spp. began in 1911 when it was isolated from a soil sample and named Micrococcus calcoaceticus (Henriksen [1]). Only in 1971 was the genus Acinetobacter officially recognized by taxonomists based on shared biochemical features [1][2][3]. The name of this genus comes from the Greek word a-kinetos-bacter which means non-motile rod, although they do exhibit a coccobacillary morphology and twitching motility. To date, molecular approaches have allowed identification of over 65 validly published species within the Acinetobacter genus (https://lpsn.dsmz.de/genus/Acinetobacter; up to 18 March 2021). These bacteria are Gram-negative, strictly aerobic, non-fermentative, oxidase-negative, catalase-positive and non-pigmented or pale yellow to gray pigmented [4][5][6]. Closely related species displaying similar phenotypic and biochemical properties are included in the Acinetobacter calcoaceticus–Acinetobacter baumannii complex (ACB complex), including Acinetobacter calcoaceticus, Acinetobacter baumannii, Acinetobacter pittii, Acinetobacter nosocomialis, Acinetobacter seifertii and Acinetobacter dijkshoorniae for which molecular methods of identification are required [7][8][9]. Apart from A. calcoaceticus, the other five species are associated with human diseases, with A. baumannii as the commonest clinical species around the world [10]. Indeed, this opportunistic pathogen causes community and nosocomial infections, predominantly ventilator-associated pneumonia and bloodstream, urinary tract and skin and soft tissue infections, especially among critically ill patients in intensive care units (ICUs) [11]. Regrettably, the number of multidrug-resistant (MDR) A. baumannii isolates has increased significantly [12][13][14]. Apart from innate resistance to several antibiotics, A. baumannii genomic plasticity is suited for acquiring or upregulating resistance genes, thereby curtailing effective therapeutic options and increasing mortality rates [14][15]. In addition to antibiotic-resistance genes, A. baumannii has several potential virulence traits that allow this bacterium to persist in the environment, adhere to biotic surfaces, invade host cells and escape from the human host immune system [11][16][17][18][19]. While several reviews have described the mechanisms of antibiotic resistance and ability to form biofilms on abiotic surfaces, fewer studies have focused on host–A. baumannii interactions.

2. A. baumannii Pan-Genomics, Genomics and Genome Plasticity

As the number of A. baumannii infections increased, it was immediately clear that isolates displayed a remarkable difference in antibiotic profile. Therefore, several investigations were focused on genotypic and phenotypic characterizations of A. baumannii isolates due to the global high rate of infections and the paucity of therapeutic options for MDR strains. Two multilocus sequence typing (MLST) schemes were introduced to study the relationships among A. baumannii isolates [20][21] (https://pubmlst.org/organisms/Acinetobacter-baumannii) (accessed on 18 March 2021). These analyses highlighted the distribution and spread of different bacterial lineages. MLST showed a specific geographical distribution for each of the different lineages as a consequence of A. baumannii isolates that underwent local expansions. Currently, among the nine international clones (ICs) identified, IC-I and -II predominate in terms of outbreaks across continents [22][23][24][25]. However, despite its advantages, MLST has provided limited information to infer the genetic relationship among the increasing number of A. baumannii isolates [15][26]. With new sequencing technologies, the study of the whole genomes has improved significantly. This approach provided the opportunity to understand the extent of the genomic heterogeneity among A. baumannii isolates, in terms of insertions, deletions, inversions and single nucleotide polymorphisms [22][23][24]. The considerable genetic differences reflect A. baumannii’s high genome plasticity that allows acquisition of exogenous genetic information, mostly via horizontal gene transfer and allelic recombination at specific hotspots, along with the loss of unnecessary genes [24][27][28][29]. These data corroborate the knowledge that A. baumannii isolates display a high degree of gene diversity to better adapt to new niches; the bacterial environmental or pathogenic lifestyle drives genetic differences, considering environmental strains those mainly isolated in hospitals (i.e., inert surfaces) and pathogenic strains those associated with the human host. To gain insights into A. baumannii adaptation to specific niches, most studies have focused on its pangenome. Up to March 2021, a total of 5076 A. baumannii genome sequences are available in the NCBI database (www.ncbi.nlm.nih.gov/) (accessed on 18 March 2021). Pangenome encompasses both core and accessory genomes; the core defines the genes commonly shared by all strains included in the analysis, whereas the accessory includes genes retrieved in one (unique gene families) or some strains. A recent work estimated that A. baumannii core genome consists of around 2200 genes, whereas the pangenome is notably larger harboring over 19,000 different genes [30]. By analyzing the shared set of genes among 2467 genomes, Mangas et al. distinguished two main A. baumannii groups; the first group, accounting for 34% of investigated A. baumannii strains, rarely carries plasmids and is characterized by clustered regularly interspaced short palindromic repeat (CRISPR), CRISPR-associated (cas) or restriction-modification system (rms) genes, and prokaryotic toxin-antitoxin systems (TASs) [30]. TASs are important virulence factors in stressful environmental conditions since they are involved in cellular metabolism, growth activities such as cell cycle process and apoptosis [31][32][33]. Conversely, the second group, accounting for the majority of investigated A. baumannii strains (66%) shared a higher number of genes, annotated as plasmid genes with exonuclease activity whereas a limited content of genes involved in biofilm formation was found [30]. It was recently suggested that the presence of CRISPR/Cas systems reduces the acquisition rate of antibiotic resistance genes, being negatively associated with A. baumannii MDR isolates [34]. Hence, it can be hypothesized that environmental strains are characterized by the presence of CRISPR/Cas systems that positively influence biofilm production to enhance persistence and inhibit the acquisition of foreign DNA, including antibiotic resistance genes. Vice versa, human-associated strains lose the CRISPR/Cas systems to evolve more easily into MDR strains and reside in antibiotic rich niches. Moreover, if iron acquisition systems are considered, isolates collected from infected samples show a set of genes required for the biosynthesis of acinetobactin, whereas the same set of genes is missing from environmental samples which, in turn, have genes involved in the uptake of iron through xeno-siderophores [35].

Overall, the more that data are acquired from genome sequencing of A. baumannii strains, the higher the heterogeneity found among them as a consequence of their high genome plasticity. However, this approach highlighted the genomic divergence of environmental and human-associated strains; although genome sequencing data are biased by the larger number of clinical isolates, it seems that unique strain-specific gene pool arises from genetic changes driven by niche variations [9][21][23][24][27]. Further genome comparison analyses between nonclinical and clinical isolates will help our understanding about the evolutionary process of A. baumannii as well as antibiotic-resistance spread and nosocomial persistence.

3. A. baumannii and the Treasure of its Virulome

Despite being an opportunistic pathogen, the A. baumannii mortality rate of patients with hospital- and community-acquired infections is 23–68% and up to 64%, respectively [11]. Being a major cause of infections, A. baumannii belongs to the ESKAPE group together with Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa and Enterobacter species [36]. The high mortality rate is tightly associated with the worldwide rise in the number of carbapenem-colistin-resistant A. baumannii strains [11]. Due to the paucity of therapeutic options in the treatment of A. baumannii infections, in 2017 the World Health Organization (WHO) placed this microorganism in the critical priority list of bacteria that urgently require the development of effective drugs as well as alternative strategies (www.who.int) (accessed on 18 March 2021). Since recent papers provide detailed coverage of the genes and mechanisms used by A. baumannii to gain resistance to antibiotics, including carbapenems and colistin, this topic will not be discussed in detail and the reader is referred to [37][38][39]. To improve our knowledge of A. baumannii pathogenesis and develop new strategies to combat infections, several studies investigated its virulence factors [11][18][40][41][42]. Remarkably, A. baumannii has a huge pathogenic potential that enables it to firmly resist in the environment, form biofilms, move, interact with host cells, capture micronutrients, and secrete proteins [3][13][16][18][41][42][43][44]. An overview of the virulence factors described in this review is presented in Table 1.

Table 1. Overview of A. baumannii virulence factors reported in this review.

Gene(s) Virulence Factor(s) Function(s) Reference
K locus capsule Persistence [44]
OC locus Lipo-oligosaccharide (LOS) Dryness resistance [45]
csuA/BABCDE Csu pili Biofilm formation [46]
bap Bap Biofilm formation [47]
M215_09430 locus Repeats-in-Toxin (RTX)-like domain Biofilm formation [12]
pgaABCD locus PNAG Biofilm formation [48]
recA RecA DNA damage repair [49]
katG KatG Oxidative stress resistance [50]
katE KatE Oxidative stress resistance [50]
abuO AbuO (component of an ABC efflux pump) Oxidative stress response [51]
adeABC AdeABC
(RDN efflux pump)		 Osmotic stress resistance [52]
emrAB EmrAB
(MFS efflux pump)		 Osmotic stress resistance [53]
abeD AbeD
(component of an RND-type efflux pump)		 Osmotic stress resistance [54]
amvA AmvA (component of an MFS efflux pump) Resistance to disinfectants [55]
aceI AceI (component of a PACE efflux pump) Resistance to disinfectants [56]
abaI AbaI (component of the QS system) Virulence, motility, conjugation, biofilm formation and host-pathogen interactions [57]
abaR AbaR (component of the QS system) Virulence, motility, conjugation, biofilm formation and host-pathogen interactions [57]
bfmS BfmS QS-regulated two-component system involved in biofilm formation [58]
bfmR BfmR QS-regulated two-component system involved in biofilm formation [58]
pilA PilA
(major pilin of type IV pili)		 Twitching motility and evasion of the host immune system [59]
ompA OmpA Antibiotic- and serum-resistance, biofilm formation, host-interaction, cytotoxicity, interference with autophagy and apoptosis [60][61][62][63][64][65][66][67]
carO CarO Resistance to carbapenems [68][69][70]
omp33 Omp33
(also known as Omp33-36 kDa or Omp34)		 Induction of apoptosis and modulation of autophagy [71][72]
occAB1 OccAB1
(also known as OprD-like or porinD)		 Uptake of antibiotics and iron, host-interaction [70][73][74][75][76]
ompW OmpW Iron uptake and cytoxicity [77]
Acinetobactin gene cluster Acinetobactin Iron chelator [78]
Fimsbactins gene cluster Fimsbactins A-F Iron chelators [78]
Baumannoferrin gene cluster Baumannoferrin A-B Iron chelators [78]
fur Fur Iron metabolism transcriptional regulator [79]
plc1 and plc2 PLC Lipolytic activity for iron acquisition [80]
pld1-3 PLD Lipolytic activity for iron acquisition [81]
oxyR OxyR ROS response regulator [82]
soxR SoxR Superoxide response regulator [83]
znuA, znuCB, znuD1 and znuD2 ZnuA, ZnuB, ZnuC, ZnuD1 and ZnuD2 Uptake of zinc [84]
zur Zur Zinc metabolism transcriptional regulator [84]
zigA ZigA Zinc metallo-chaperone [85]
mumT MumT Uptake of manganese [86]
pit PIT system Low affinity phosphate uptake system [87]
pst operon PstS High affinity phosphate uptake system [88]
phoB and phoR PhoB and PhoR Two-component regulatory system for phosphate uptake [89]
hlyB, hlyD and tolC HlyB, HlyD and TolC
(T1SS)		 Secretion of proteins involved in biofilm formation and adhesion to pulmonary epithelia [12]
gsp genes T2SS Secretion of proteins from the Sec or the Tat translocons [90]
tra locus T4SS Conjugative transfer of DNA, plasmids, and other mobile genetic elements [91]
AbfhaB and AbfhaC AbFhaB and C
(T5bSS)		 Adhesion to integrin and fibronectin [92]
cdiA1, cdiB1, cdiA2 and cdiB2 CdiA and B
(T5bSS)		 Killing of bacterial competitors [93]
ata Ata
(T5cSS)		 Adhesion to collagen I, III, IV, V and laminin [94]
Core, accessory and regulatory genes T6SS Contact-dependent secretion of substrates into competitor bacterial or eukaryotic cells [95]
None OMVs Long-distance delivery of multiple packaged virulence factors [96]

3.1. Survival Strategies

The environmental survival of A. baumannii depends on its ability to persist against desiccation, disinfection and oxidative stresses. Besides other important functions, the biosynthesis of capsular polysaccharide and biofilm formation support the viability of A. baumannii in dry conditions for over three months [18][43][97][98]. The K locus encompasses clustered genes needed for the biosynthesis of the capsule [44][99]. Despite strain-specific biosynthetic genes accounting for the wide diversity of capsule composition, the K locus commonly includes genes encoding initiating transferases (itr), glycosyltransferases (gtr), assembly/export proteins (wzx/wzy), and modification enzymes (atr/ptr) [13]. The polysaccharides composing the capsule act as water retainers that shield the bacterial body against desiccation [100]; however, although mutant strains within the K locus displayed lower resistance, the heterogeneous behavior of encapsulated bacteria in relation to desiccation led to the conclusion that the capsule plays a minor role [100]. The lipid composition of the outer membrane, more specifically the acylated level of the lipo-oligosaccharide (LOS), has been suggested to be involved in resistance to dryness, in that the appropriate fluidity retains water and nutrients inside the bacterial cell [45][101]. Indeed, in A. baumannii, the common bacterial lipopolysaccharide is replaced with the LOS, which is composed of lipid A with variable amounts of inner and outer core sugars but lacks the O-antigen [45]. The LOS outer sugars show diversity across strains, dependent on glycosyltransferases and nucleotide-sugar biosynthesis enzymes encoded in a highly variable outer core locus [13].

The ability to form biofilms extends the desiccation tolerance of A. baumannii under dryness [100]. Biofilm formation starts with bacterial adherence to a surface and it is further strengthened by bacterial attachment and aggregation. These sessile bacterial communities are surrounded by a blended matrix consisting of DNA, exopolysaccharides (capsular and non-capsular) and proteins which protect pathogens from desiccation, since the exopolysaccharide matrix can retain water [100]. The Csu pili or Csu fimbriae are encoded by six-segmented operon, csuA/BABCDE, and are assembled by the chaperone–usher (CU) pathway [46]. Together with the biofilm-associated proteins (Bap), Csu pili are crucial for the formation and maintenance of biofilms on abiotic surfaces [11][16][18][46][47][102]. Some recent reviews describe the detailed network controlling biofilm formation [11][18][44][103][104][105]. Other important factors involved in biofilm formation are an effector protein encompassing a Repeats-in-Toxin (RTX)-like domain, poly-β (1-6)-N-acetyl-glucosamine (PNAG), the capsule, and autotransporter systems that will be discussed below [3][11][12][13][48]. Despite the remarkable desiccation tolerance of A. baumannii during environmental persistence, the restricted water availability could lead to DNA damages, osmotic and oxidative stresses [18][44][100]. A. baumannii copes with DNA damages, comprising alkylation, base omission, cross-linking, oxidation and strand breaks, with the RecA protein, which is recognized as an essential enzyme for homologous recombination [18][49][106]. Oxidative stress can be overcome by overexpression of genes encoding catalases. Indeed, A. baumannii is a catalase-positive bacterium; despite the genomic presence of four catalase genes, katA, katE, katG, and katX, only KatG and KatE defend the bacterium from oxidative stress [50][100]. Interestingly, both katG and katE genes are overexpressed through the upstream insertion of ISAba1 promoter sequences, thereby providing full protection from hydrogen peroxide (H2O2) [50][100]. Moreover, DNA damages as consequence of water stress, as well as other environmental stresses in clinical settings, generate base-pair substitutions in a number of different bacterial targets, thereby contributing to the acquisition of additional antibiotic resistances in A. baumannii (i.e., rifampin-resistance) [7][18][107]. Conversely, the osmoregulatory mechanism adopted by A. baumannii aims to increase the uptake of glycine betaine or synthesize glutamate and mannitol; without interfering with the general bacterial metabolism, these compounds, known as compatible solutes, stabilize proteins and membranes, thereby protecting bacteria from cell damage [18][100]. Osmotic stress, desiccation and resistance to antibiotics and disinfectants also involve efflux pumps, three-component protein systems (an outer membrane channel, a periplasmic lipoprotein, and an inner membrane transporter) that extrude disturbing or toxic molecules/compounds from inside the cell to the extracellular milieu. A. baumannii possesses several classes of efflux pumps, including major facilitator superfamily (MFS), resistance nodulation-division (RND), small multidrug resistance (SMR) family, and multidrug and toxic efflux (MATE), ATP binding cassette (ABC), and the proteobacterial antimicrobial compound efflux (PACE) family [53][55][108][109]. Apart from their role in antibiotic resistance, the RDN AdeABC, the MFS EmrAB efflux pumps as well as the RND-type AbeD transporter contribute to osmotic stress resistance [52][53][54][100][109]. Moreover, AbuO, a TolC-like protein, is involved in the oxidative stress response [54][109]. AmvA and AceI, belonging to the MFS and PACE efflux pumps respectively, were shown to be associated with the extrusion of disinfectants [54][55][56][109][110]. It is worth mentioning that the great adaptability of A. baumannii to such a variety of different stressful environments relies on several additional proteins that guarantee cellular homeostasis, such as GroEL, GroES, DnaJ, DnaK, ClpX, ClpB, OxyR, as well as Lon protease and other numerous chaperones [111][112][113][114]. Complex regulatory networks overlook these stress defense mechanisms, including two-component systems, the second messenger cyclic-di-GMP, the RNA chaperone Hfq, alternative sigma factors of the general stress response, and quorum sensing (QS) regulators [51][54][100][103][105][109][110][115].

3.2. Sensing the Quorum

Bacterial QS is a cell-to-cell communication system based on specific signaling molecules called ‘auto-inducers’ that allow bacteria to sense population densities. QS systems have a crucial role in the expression of virulence factors, motility, conjugation, biofilm formation and interactions with eukaryotic host cells [16][104][116][117][118]. To date, only one QS system was found in A. baumannii, consisting of the two abaI and abaR genes, acquired from Halothiobacillus neapolitanus through horizontal gene transfer. AbaI is the autoinducer synthase and AbaR is its cognate receptor, which belong to the typical LuxI/LuxR family members found in other Gram-negative bacteria. AbaI synthesizes N-(3-hydroxydodecanoyl)-1-homoserine lactone (Acyl Homo-serine Lactones, AHLs); upon binding of AHL to AbaR, the complex recognizes lux-box sequences on QS target promoters, thereby regulating their expression [57][119]. Indeed, QS molecules affect A. baumannii bfmS and bfmR genes by upregulating their expression leading to strong biofilm formation on abiotic surfaces [16][58]. Limited concentrations of iron also upregulate QS signaling molecules, enhancing A. baumannii persistence and virulence [16][119][120].

3.3. The Power of Pilus Retraction

Despite the name of this genus, A. baumannii is able to perform twitching motility through type IV pili. Encoded by the pil operon genes, these pili are cytoplasmic ATPase dependent projections that extend and retract to keep the bacterium going, mainly on wet surfaces [102]. It has been shown that the C-terminus of the major subunit of type IV pili, PilA, is glycosylated by O-oligo-saccharyl-transferases [59]. Interestingly, there is a high degree of variability both in amino acid sequence as well as in glycosylation of PilA proteins among A. baumannii isolates, most probably to evade the host immune system [121]. Although a clear link between twitching motility and virulence has not yet been established, several studies showed an upregulated biogenesis of type IV pili when grown in serum with respect to sputum, highly suggestive of a key role of twitching motility during bacteremia [13][18][44]. However, the role of type IV pili is not restricted to twitching motility but also to biofilm formation, virulence and DNA uptake [13][18][44][59]. Indeed, it has been reported that type IV pili promote host-cell adhesion to both pharynx and lung carcinoma cells in vitro [121]. In addition to twitching motility, some isolates of A. baumannii can move by surface-associated motility [13][18][44]. This motility seems to be independent from type IV pili and relies on the biosynthesis of polyamine 1,3-diaminopropane, LOS and QS [13][18][44]. Although the precise mechanism of surface-associated motility remains to be elucidated, the signaling network of cyclic-di-GMP, the second messenger molecule involved in adaptation to various stress responses, was shown to upregulate biofilm formation and downregulate surface associated motility [105].

3.4. Exploring Surface Proteins

Outer membrane proteins (Omps) embedded within the outer membrane (OM) are cornerstone proteins involved in cellular permeability and virulence in A. baumannii. These monomeric or trimeric β-barrel proteins, also known as porins, connect the external environment to the periplasmic space, allowing the diffusion of nutrients as well as small molecules, antibiotics, and disinfectants [18][40][41][44][51]. To date, identified Omps in A. baumannii are OmpA, CarO, OprD-like, Omp33-36 kDa, OmpW, AbuO, TolB, DcaP, Oma87/BamA, NmRmpM, CadF, OprF, LptD [18][41][44]. Besides its role in antibiotic-resistance, OmpA plays a central role in A. baumannii virulence, including, serum resistance, biofilm formation, host-interaction, cytotoxicity, and apoptosis [11][18][60][61][62][63][64][65][66][67][122]. OmpA has eight- antiparallel β-barrel strands embedded within the OM at the N-terminus while the C-terminus is bound to a peptidoglycan-derived pentapeptide, thereby performing also a structural role [123]. The amino acid sequence of this protein is highly conserved among A. baumannii clinical isolates; its involvement in antibiotic-resistance was revealed by the use of ompA mutants [41][62]. However, the increase in antibiotic-susceptibility of these mutants could be related to a broader membrane permeability as a consequence of membrane alterations [61]. Nevertheless, several studies demonstrated that OmpA acts as a specific and selective channel for small antibiotics [41][61][62][124]. However, multiple data indicate that OmpA is associated with efflux pump systems located in the inner membrane to counteract the influx of antibiotics [62]. Due to its key role, several proteins control ompA expression such as the global repressor H-NS and an anti-repressor (i.e., gene locus A1S_0316), the RNA chaperone Hfq as well as the two-component system BfmSR [41][125][126]. Its high amino acid conservation among isolates, crucial structural role and strong immunogenicity make OmpA the ideal target for the development of an A. baumannii vaccine [124]. Additionally, several studies have addressed the role of CarO or carbapenem susceptibility porin in A. baumannii [13][41][68][69][70]. Limansky et al. first demonstrated that resistance to carbapenems among clinical isolates, specifically to imipenem, was due to the loss of CarO [127]. CarO is the channel for the transport of small amino acids such as glycine and ornithine, but it was shown to mediate the influx of imipenem into the bacterial cells [13][41]. While this may seem very harmful, CarO physically interacts with the most widespread carbapenemase OXA-23 in A. baumannii so that imipenem is hydrolyzed immediately upon entry into the bacterial periplasm [128]. Additionally, five porins orthologous to OprD from P. aeruginosa were identified in carbapenem-resistant A. baumannii isolates; they belong to the Occ class (OccAB1–5) [129]. Structural studies of OccAB1–4 showed that they are 18-stranded β-barrel proteins characterized by different pore diameters; OccAB1 has the largest channel and was the most efficient in the uptake of carbapenems [70][73][74][75][76][129]. Formerly known as porinD or OprD, this protein was showed to be involved in the transport of different molecules including amino acids, sugars and antibiotics such as meropenem and Fosfomycin [129]. Moreover, OprD together with OmpW were linked to iron uptake in A. baumannii [77]. OmpW is an eight-stranded OM β barrel protein that shares several features with OmpA; its amino acid sequence is highly conserved among A. baumannii isolates, it is greatly immunogenic, highly concentrated in OM vesicles (OMVs) and it has cytotoxic activity against host cells [63][77][130]. OMVs are micro-spherical vesicles of 20-200 nm in diameter that are secreted by the secretory system independently from conventional systems [11][42][63][96][131][132]. These vesicles are composed of LOS, Omps, phospholipids, periplasmic proteins, as well as DNA and RNA molecules; OMVs are a means through which bacteria deliver a number of bacterial virulence factors to other bacteria or host cells, thereby inducing host cell damage and innate immune responses [7][11][13][19][42][63]. Another important Omp in A. baumannii is Omp33-36 kDa or Omp34 or Omp33 [41][71][72]. Its resolved crystal structure showed that Omp33 has 14 antiparallel β-strands connected by 7 loops extending outside and 6 turns protruding into the periplasmic side; recently, it was reported that two of these periplasmic turns block the aqueous channel [41]. Interestingly, it was found that Omp33 plays an important role in fitness and virulence in A. baumannii; this cytotoxic protein triggers apoptosis via caspase activation while modulating autophagy to enhance its persistence within host cells [71][72].

3.5. Micronutrients Hunger

Micronutrients are fundamental for bacterial survival and growth. A. baumannii possesses different metal uptake systems for scavenging zinc, iron and manganese as well as other valuable and essential nutrients. Iron bioavailability is scarce both in the environment and in hosts. To acquire free iron, A. baumannii produces and secretes siderophores, low molecular weight iron scavengers (400–1000 kDa) able to chelate it at high affinity. The catechol-hydroxy-mate siderophores including acinetobactin, fimsbactins A-F, baumannoferrin A and B are examples of A. baumannii iron chelators [78]. However, acinetobactin is the most conserved and recognized siderophore in A. baumannii [7][11][18][133]. According to genomic studies, bacterial siderophore biosynthetic genes are usually clustered and under the transcriptional control of the ferric uptake regulator Fur encoded by the fur gene [11][79][114]. Due to the importance of iron in A. baumannii physiology, the expression of a huge number of genes is under the control of iron availability, including those encoding for efflux pumps belonging to MFS, MATE, and ABC families, QS, Bap, phospholipases C and D, catalase and superoxide dismutase [51][54][55][80][81][108][109][110][134]. Indeed, to overcome the high reactivity of iron via the Fenton reaction, iron acquisition and metabolism is associated with the expression of OxyR and SoxR, responsible for reactive oxygen species (ROS) detoxification and for super oxide response, respectively [11][18][82][83][111][135][136]. A. baumannii phospholipases C and D are potent virulence factors characterized by hydrolytic and lipolytic activities; these enzymes showed hemolytic activities by targeting red blood cells in order to provide iron for A. baumannii growth during the infection process [7][11][18][133][136]. In addition, iron receptors or transport proteins that bind directly ferrous (Fe2+) ions are located on the bacterial cell surface [11]. In addition to iron, zinc (Zn) and manganese (Mn) are important micronutrients for growth and virulence in A. baumannii. Being a cofactor of metalloproteins, e.g., metalloproteases, A. baumannii employs an ABC transporter system, ZnuABC that works together with the OM TonB-dependent receptor ZnuD for the uptake of zinc; the whole system is under the control of the transcriptional zinc uptake regulator Zur [84][137]. Thereafter, the Zn metallochaperone ZigA seems to assist the transfer of the precious metal to metalloproteins, although more studies are required to elucidate the precise mechanism [11][18][85][136]. Mn is the redox-active cofactor for enzymes that protect the bacteria from ROS, such as superoxide dismutase and ribonucleotide reductase [11][42]. Like other pathogens, A. baumannii has a high-affinity Mn transmembrane transporter, MumT, belonging to the resistance-associated macrophage protein (NRAMP) family, that uses the proton motive force as an energy source for the uptake of exogenous manganese [86][111][138]. Being involved in several biochemical reactions, phosphate has two dedicated transport systems in A. baumannii, a low- and a high-affinity transport system, encoded by the pit gene and the pst operon (pstA, pstB, pstC, pstS, and phoU), respectively [87][88]. In this latter, the periplasmic phosphate-binding protein PstS controls the system by sensing phosphate levels and by transferring it to its specific transporter; the whole operon is transcriptionally activated by the two-component system PhoB/R under phosphate deficiency [89][139]. Interestingly, it was recently reported that PstS plays an important role in A. baumannii virulence during microaerobic conditions; indeed, the pstS deletion mutant showed reduced adhesion to and invasion of human alveolar type II cells (A549 cell line, see below), whereas its overexpression enhances pathogenesis [88]. Supported also by in vivo results, it was concluded that PstS is important for A. baumannii pathogenicity and spread within the host [88].

3.6. The Versatility of Secretion Systems

Bacteria secrete proteins to adapt more easily to environmental conditions and host-interactions. To date, five secretion systems have been identified in A. baumannii, comprising type 1 secretion system (T1SS), T2SS, T4SS, T5SS, and T6SS [11][18][44]. T1SS is composed by an inner membrane (IM) ATPase protein (hemolysin secretion protein B, HlyB), a periplasmic adaptor (hemolysin secretion protein D, HlyD), and an Omp (TolC); this system contributes to exporting proteins involved in biofilm formation and maintenance and assisting also to adhesion with pulmonary epithelia, i.e., Bap and Blp1, as well as the RTX-serra-lysin-like toxin [12][140]. Conversely, the T2SS involves 12–15 proteins including cytoplasmic ATPases, IM platform assembly, OM secretins and periplasmic pseudo-pili; the pseudo-pilus works as a sort of piston that extrudes substrates out of the bacterial cells though OM secretins. Genes encoding the proteins composing T2SS are referred to as general secretory pathway (Gsp) [90][141]. T2SS accommodates proteins with an export signal from the Sec or the Twin-arginine (Tat) translocons before delivering them outside the cell; important virulence factors such as lipases (LipA and LipH), zinc-dependent metallo-endopeptidase (CpaA), elastase, alkaline phosphatase, and phospholipases are secreted by T2SS [3][13]. Interestingly, T2SS and type IV pili share the pilin peptidase PilD/GspO that processes pre-pseudo-pilins and pre-pilins before assembly into the T2SS and type IV pilus, respectively, revealing their evolutionary relatedness [141][142]. T4SS (type F) is devoted to conjugative transfer of DNA, plasmids, and other mobile genetic elements; therefore, this system is thought to be responsible for the spread of antibiotic-resistance genes among A. baumannii clinical isolates and particularly OXA- 23 [44][91][143]. Conversely, the T5SS, also known as autotransporters, represents the simplest and most widespread secretion system in Gram-negative bacteria; the name is due to the ability of these proteins to cross the OM autonomously [144][145]. T5SS is composed of five subgroups, T5aSS, T5bSS, T5cSS, T5dSS and T5eSS [145]. This classification is based on the specific features of the passenger/translocation domains, quaternary structure (i.e., monomeric or trimeric), and the terminal residues of proteins exposed on the surface (N- or C-terminus) [145]. Only the T5bSS (AbFhaB/C and CdiA/B) and T5cSS (Ata) subgroups were found in A. baumannii [11][92][93]. In the T5bSS subclass, also termed the two-partner secretion (TPS) system, passenger and translocation domains (TpsA and TpsB, respectively) are allocated onto two distinct proteins whose genes are transcriptionally linked [11]. The 16-stranded β barrel AbFhaC protein recognizes and translocates to the cell surface its partner protein, AbFhaB, via two specific periplasmic polypeptide transport-associated domains; AbFhaB has the arginine-glycine-aspartic acid (RGD) motif that was shown to be associated with eukaryotic integrin and fibronectin attachment [92]. The contact-dependent inhibition (CDI) systems are strategies that A. baumannii uses to kill bacterial competitors; the OM pore CdiB allows the secretion of the CdiA toxin that kills bacterial cells that do not have the antitoxin or the immunity protein CdiI [3]. A. baumannii has two CDI loci, Cdi1 and Cdi2, each composed of the transporter, the toxin and the immunity proteins [42]. On the other hand, Acinetobacter trimeric autotransporter, or Ata, belongs to the T5cSS; each monomer of this large homo-trimeric protein consists of a C-terminal domain that forms a 4 β-strand hydrophilic pore within the OM through which it extrudes the N-terminal passenger domain of each monomer [94]. The passenger domain contains four pentameric collagen binding consensus sequences (SVAIG) and one RGD motif able to bind extracellular matrix and basal proteins (i.e., collagen I, III, IV, and V and laminin) and to participate to biofilm formation [94]. Finally, several A. baumannii strains carry a genetic locus for T6SS; this contact-dependent multi-component apparatus is encoded by 13 core structural proteins together with accessory (i.e., TagF, TagN, PAAR, and TagX) and regulatory proteins (i.e., VgrG1, TetR) [95]. Indeed, due to the high-demanding energy costs, T6SS is activated upon stressful stimuli, including nutrient limitation, cell damage and competing bacteria [146]. Accordingly, the T6SS enables A. baumannii to inject into other bacteria toxic proteins, including peptidoglycan hydrolases, nucleases, or those effectors targeting the cell membrane, to outcompete neighboring bacteria [147].

It is important to note that in the past, A. baumannii was considered a commensal, and a relatively low-grade opportunistic pathogen; the main features of A. baumannii virulence factors highlighted the great pathogenic potential of this bacterium. Nevertheless, it should be taken into account that the immune status of the human host plays a big role in the infective success of A. baumannii. In the following paragraphs, the components of A. baumannii virulome important for the interaction with host cells and evasion of the host immune response will be discussed.

References

  1. Henriksen, S.D. Moraxella, Acinetobacter, and the Mimeae. Bacteriol. Rev. 1973, 37, 522–561.
  2. Baumann, P.; Doudoroff, M.; Stanier, R.Y. A study of the Moraxella group. II. Oxidative-negative species (genus Acinetobacter). J. Bacteriol. 1968, 95, 1520–1541.
  3. Elhosseiny, N.M.; Attia, A.S. Acinetobacter: An emerging pathogen with a versatile secretome. Emerg. Microbes Infect. 2018, 7, 1–15.
  4. Gonzalez-Villoria, A.M.; Valverde-Garduno, V. Antibiotic-Resistant Acinetobacter baumannii Increasing Success Remains a Challenge as a Nosocomial Pathogen. J. Pathog. 2016, 2016, 7318075.
  5. Visca, P.; Seifert, H.; Towner, K.J. Acinetobacter infection–an emerging threat to human health. IUBMB Life 2011, 63, 1048–1054.
  6. Wong, D.; Nielsen, T.B.; Bonomo, R.A.; Pantapalangkoor, P.; Luna, B.; Spellberg, B. Clinical and Pathophysiological Overview of Acinetobacter Infections: A Century of Challenges. Clin. Microbiol. Rev. 2017, 30, 409–447.
  7. Lee, C.-R.; Lee, J.H.; Park, M.; Park, K.S.; Bae, I.K.; Kim, Y.B.; Cha, C.-J.; Jeong, B.C.; Lee, S.H. Biology of Acinetobacter baumannii: Pathogenesis, antibiotic resistance mechanisms, and prospective treatment options. Front. Cell. Infect. Microbiol. 2017, 7, 55.
  8. Li, Y.; Yang, X.; Zhao, W. Emerging microtechnologies and automated systems for rapid bacterial identification and antibiotic susceptibility testing. SLAS Technol. Transl. Life Sci. Innov. 2017, 22, 585–608.
  9. Vijayakumar, S.; Biswas, I.; Veeraraghavan, B. Accurate identification of clinically important Acinetobacter spp.: An update. Future Sci. OA 2019, 5, Fso395.
  10. Cerqueira, G.M.; Peleg, A.Y. Insights into Acinetobacter baumannii pathogenicity. IUBMB Life 2011, 63, 1055–1060.
  11. Morris, F.C.; Dexter, C.; Kostoulias, X.; Uddin, M.I.; Peleg, A. The mechanisms of disease caused by Acinetobacter baumannii. Front. Microbiol. 2019, 10, 1601.
  12. Harding, C.M.; Pulido, M.R.; Di Venanzio, G.; Kinsella, R.L.; Webb, A.I.; Scott, N.E.; Pachón, J.; Feldman, M.F. Pathogenic Acinetobacter species have a functional type I secretion system and contact-dependent inhibition systems. J. Biol. Chem. 2017, 292, 9075–9087.
  13. Geisinger, E.; Huo, W.; Hernandez-Bird, J.; Isberg, R.R. Acinetobacter baumannii: Envelope determinants that control drug resistance, virulence, and surface variability. Annu. Rev. Microbiol. 2019, 73, 481–506.
  14. Gallagher, P.; Baker, S. Developing new therapeutic approaches for treating infections caused by multi-drug resistant Acinetobacter baumannii: Acinetobacter baumannii therapeutics. J. Infect. 2020, 81, 857–861.
  15. Hua, X.; Zhang, L.; He, J.; Leptihn, S.; Yu, Y. Population Biology and Epidemiological Studies of Acinetobacter baumannii in the Era of Whole Genome Sequencing: Is the Oxford Scheme Still Appropriate? Front. Microbiol. 2020, 11, 775.
  16. Eze, E.C.; Chenia, H.Y.; El Zowalaty, M.E. Acinetobacter baumannii biofilms: Effects of physicochemical factors, virulence, antibiotic resistance determinants, gene regulation, and future antimicrobial treatments. Infect. Drug Resist. 2018, 11, 2277.
  17. García-Patiño, M.G.; García-Contreras, R.; Licona-Limón, P. The immune response against Acinetobacter baumannii, an emerging pathogen in nosocomial infections. Front. Immunol. 2017, 8, 441.
  18. Harding, C.M.; Hennon, S.W.; Feldman, M.F. Uncovering the mechanisms of Acinetobacter baumannii virulence. Nat. Rev. Microbiol. 2018, 16, 91.
  19. Pires, S.; Parker, D. Innate Immune Responses to Acinetobacter baumannii in the Airway. J. Interferon Cytokine Res. Off. J. Int. Soc. Interferon Cytokine Res. 2019, 39, 441–449.
  20. Bartual, S.G.; Seifert, H.; Hippler, C.; Luzon, M.A.; Wisplinghoff, H.; Rodríguez-Valera, F. Development of a multilocus sequence typing scheme for characterization of clinical isolates of Acinetobacter baumannii. J. Clin. Microbiol. 2005, 43, 4382–4390.
  21. Diancourt, L.; Passet, V.; Nemec, A.; Dijkshoorn, L.; Brisse, S. The population structure of Acinetobacter baumannii: Expanding multiresistant clones from an ancestral susceptible genetic pool. PLoS ONE 2010, 5, e10034.
  22. Peleg, A.Y.; Seifert, H.; Paterson, D.L. Acinetobacter baumannii: Emergence of a successful pathogen. Clin. Microbiol. Rev. 2008, 21, 538–582.
  23. Imperi, F.; Antunes, L.C.; Blom, J.; Villa, L.; Iacono, M.; Visca, P.; Carattoli, A. The genomics of Acinetobacter baumannii: Insights into genome plasticity, antimicrobial resistance and pathogenicity. IUBMB Life 2011, 63, 1068–1074.
  24. Antunes, L.C.; Visca, P.; Towner, K.J. Acinetobacter baumannii: Evolution of a global pathogen. Pathog. Dis. 2014, 71, 292–301.
  25. Müller, C.; Stefanik, D.; Wille, J.; Hackel, M.; Higgins, P.G.; Seifert, H. Molecular epidemiology of carbapenem-resistant Acinetobacter baumannii clinical isolates and identification of the novel international clone IC9: Results from a worldwide surveillance study (2012–2016). In Proceedings of the Abstract Book of the 29th European Congress of Clinical Microbiology and Infectious Diseases, P0947, Amsterdam, The Netherlands, 13–16 April 2019.
  26. Castillo-Ramírez, S.; Graña-Miraglia, L. Inaccurate Multilocus Sequence Typing of Acinetobacter baumannii. Emerg. Infect. Dis. 2019, 25, 186–187.
  27. Galac, M.R.; Snesrud, E.; Lebreton, F.; Stam, J.; Julius, M.; Ong, A.C.; Maybank, R.; Jones, A.R.; Kwak, Y.I.; Hinkle, K.; et al. A Diverse Panel of Clinical Acinetobacter baumannii for Research and Development. Antimicrob. Agents Chemother. 2020, 64.
  28. Holt, K.; Kenyon, J.J.; Hamidian, M.; Schultz, M.B.; Pickard, D.J.; Dougan, G.; Hall, R. Five decades of genome evolution in the globally distributed, extensively antibiotic-resistant Acinetobacter baumannii global clone 1. Microb. Genom. 2016, 2, e000052.
  29. Touchon, M.; Cury, J.; Yoon, E.J.; Krizova, L.; Cerqueira, G.C.; Murphy, C.; Feldgarden, M.; Wortman, J.; Clermont, D.; Lambert, T.; et al. The genomic diversification of the whole Acinetobacter genus: Origins, mechanisms, and consequences. Genome Biol. Evol. 2014, 6, 2866–2882.
  30. Mangas, E.L.; Rubio, A.; Álvarez-Marín, R.; Labrador-Herrera, G.; Pachón, J.; Pachón-Ibáñez, M.E.; Divina, F.; Pérez-Pulido, A.J. Pangenome of Acinetobacter baumannii uncovers two groups of genomes, one of them with genes involved in CRISPR/Cas defence systems associated with the absence of plasmids and exclusive genes for biofilm formation. Microb. Genom. 2019, 5, e000309.
  31. Ghafourian, S.; Good, L.; Sekawi, Z.; Hamat, R.A.; Soheili, S.; Sadeghifard, N.; Neela, V. The mazEF toxin-antitoxin system as a novel antibacterial target in Acinetobacter baumannii. Mem. Inst. Oswaldo Cruz 2014, 109, 502–505.
  32. Lee, K.-Y.; Lee, B.-J. Structure, biology, and therapeutic application of toxin–antitoxin systems in pathogenic bacteria. Toxins 2016, 8, 305.
  33. Lobato-Márquez, D.; Díaz-Orejas, R.; García-del Portillo, F. Toxin-antitoxins and bacterial virulence. FEMS Microbiol. Rev. 2016, 40, 592–609.
  34. Tyumentseva, M.; Mikhaylova, Y.; Prelovskaya, A.; Tyumentsev, A.; Petrova, L.; Fomina, V.; Zamyatin, M.; Shelenkov, A.; Akimkin, V. Genomic and Phenotypic Analysis of Multidrug-Resistant Acinetobacter baumannii Clinical Isolates Carrying Different Types of CRISPR/Cas Systems. Pathogens 2021, 10, 205.
  35. Yakkala, H.; Samantarrai, D.; Gribskov, M.; Siddavattam, D. Comparative genome analysis reveals niche-specific genome expansion in Acinetobacter baumannii strains. PLoS ONE 2019, 14, e0218204.
  36. De Oliveira, D.M.P.; Forde, B.M.; Kidd, T.J.; Harris, P.N.A.; Schembri, M.A.; Beatson, S.A.; Paterson, D.L.; Walker, M.J. Antimicrobial Resistance in ESKAPE Pathogens. Clin. Microbiol. Rev. 2020, 33.
  37. Karakonstantis, S. A systematic review of implications, mechanisms, and stability of in vivo emergent resistance to colistin and tigecycline in Acinetobacter baumannii. J. Chemother. 2021, 33, 1–11.
  38. Hamidian, M.; Nigro, S.J. Emergence, molecular mechanisms and global spread of carbapenem-resistant Acinetobacter baumannii. Microb. Genom. 2019, 5, e000306.
  39. Scribano, D.; Marzano, V.; Levi Mortera, S.; Sarshar, M.; Vernocchi, P.; Zagaglia, C.; Putignani, L.; Palamara, A.T.; Ambrosi, C. Insights into the Periplasmic Proteins of Acinetobacter baumannii AB5075 and the Impact of Imipenem Exposure: A Proteomic Approach. Int. J. Mol. Sci. 2019, 20, 3451.
  40. Ambrosi, C.; Scribano, D.; Aleandri, M.; Zagaglia, C.; Di Francesco, L.; Putignani, L.; Palamara, A.T. Acinetobacter baumannii Virulence Traits: A Comparative Study of a Novel Sequence Type with Other Italian Endemic International Clones. Front. Microbiol. 2017, 8, 1977.
  41. Uppalapati, S.R.; Sett, A.; Pathania, R. The Outer Membrane Proteins OmpA, CarO, and OprD of Acinetobacter baumannii Confer a Two-Pronged Defense in Facilitating Its Success as a Potent Human Pathogen. Front. Microbiol. 2020, 11, 589234.
  42. Li, F.J.; Starrs, L.; Burgio, G. Tug of war between Acinetobacter baumannii and host immune responses. Pathog. Dis. 2018, 76, ftz004.
  43. Singh, J.K.; Adams, F.G.; Brown, M.H. Diversity and function of capsular polysaccharide in Acinetobacter baumannii. Front. Microbiol. 2019, 9, 3301.
  44. Ayoub Moubareck, C.; Hammoudi Halat, D. Insights into Acinetobacter baumannii: A Review of Microbiological, Virulence, and Resistance Traits in a Threatening Nosocomial Pathogen. Antibiotics 2020, 9, 119.
  45. Kenyon, J.J.; Nigro, S.J.; Hall, R.M. Variation in the OC locus of Acinetobacter baumannii genomes predicts extensive structural diversity in the lipooligosaccharide. PLoS ONE 2014, 9, e107833.
  46. Tomaras, A.P.; Dorsey, C.W.; Edelmann, R.E.; Actis, L.A. Attachment to and biofilm formation on abiotic surfaces by Acinetobacter baumannii: Involvement of a novel chaperone-usher pili assembly system. Microbiology 2003, 149 Pt 12, 3473–3484.
  47. Loehfelm, T.W.; Luke, N.R.; Campagnari, A.A. Identification and characterization of an Acinetobacter baumannii biofilm-associated protein. J. Bacteriol. 2008, 190, 1036–1044.
  48. Choi, A.H.; Slamti, L.; Avci, F.Y.; Pier, G.B.; Maira-Litrán, T. The pgaABCD locus of Acinetobacter baumannii encodes the production of poly-beta-1-6-N-acetylglucosamine, which is critical for biofilm formation. J. Bacteriol. 2009, 191, 5953–5963.
  49. Aranda, J.; Bardina, C.; Beceiro, A.; Rumbo, S.; Cabral, M.P.; Barbé, J.; Bou, G. Acinetobacter baumannii RecA protein in repair of DNA damage, antimicrobial resistance, general stress response, and virulence. J. Bacteriol. 2011, 193, 3740–3747.
  50. Monem, S.; Furmanek-Blaszk, B.; Łupkowska, A.; Kuczyńska-Wiśnik, D.; Stojowska-Swędrzyńska, K.; Laskowska, E. Mechanisms Protecting Acinetobacter baumannii against Multiple Stresses Triggered by the Host Immune Response, Antibiotics and Outside-Host Environment. Int. J. Mol. Sci. 2020, 21, 5498.
  51. Srinivasan, V.B.; Vaidyanathan, V.; Rajamohan, G. AbuO, a TolC-like outer membrane protein of Acinetobacter baumannii, is involved in antimicrobial and oxidative stress resistance. Antimicrob. Agents Chemother. 2015, 59, 1236–1245.
  52. Magnet, S.; Courvalin, P.; Lambert, T. Resistance-nodulation-cell division-type efflux pump involved in aminoglycoside resistance in Acinetobacter baumannii strain BM4454. Antimicrob. Agents Chemother. 2001, 45, 3375–3380.
  53. Lin, M.F.; Lin, Y.Y.; Lan, C.Y. Contribution of EmrAB efflux pumps to colistin resistance in Acinetobacter baumannii. J. Microbiol. 2017, 55, 130–136.
  54. Srinivasan, V.B.; Venkataramaiah, M.; Mondal, A.; Rajamohan, G. Functional Characterization of AbeD, an RND-Type Membrane Transporter in Antimicrobial Resistance in Acinetobacter baumannii. PLoS ONE 2015, 10, e0141314.
  55. Rajamohan, G.; Srinivasan, V.B.; Gebreyes, W.A. Molecular and functional characterization of a novel efflux pump, AmvA, mediating antimicrobial and disinfectant resistance in Acinetobacter baumannii. J. Antimicrob. Chemother. 2010, 65, 1919–1925.
  56. Hassan, K.A.; Jackson, S.M.; Penesyan, A.; Patching, S.G.; Tetu, S.G.; Eijkelkamp, B.A.; Brown, M.H.; Henderson, P.J.; Paulsen, I.T. Transcriptomic and biochemical analyses identify a family of chlorhexidine efflux proteins. Proc. Natl. Acad. Sci. USA 2013, 110, 20254–20259.
  57. Niu, C.; Clemmer, K.M.; Bonomo, R.A.; Rather, P.N. Isolation and characterization of an autoinducer synthase from Acinetobacter baumannii. J. Bacteriol. 2008, 190, 3386–3392.
  58. Tomaras, A.P.; Flagler, M.J.; Dorsey, C.W.; Gaddy, J.A.; Actis, L.A. Characterization of a two-component regulatory system from Acinetobacter baumannii that controls biofilm formation and cellular morphology. Microbiology 2008, 154 Pt 11, 3398–3409.
  59. Ronish, L.A.; Lillehoj, E.; Fields, J.K.; Sundberg, E.J.; Piepenbrink, K.H. The structure of PilA from Acinetobacter baumannii AB5075 suggests a mechanism for functional specialization in Acinetobacter type IV pili. J. Biol. Chem. 2019, 294, 218–230.
  60. Gaddy, J.A.; Tomaras, A.P.; Actis, L.A. The Acinetobacter baumannii 19606 OmpA protein plays a role in biofilm formation on abiotic surfaces and in the interaction of this pathogen with eukaryotic cells. Infect. Immun. 2009, 77, 3150–3160.
  61. Iyer, R.; Moussa, S.H.; Durand-Réville, T.F.; Tommasi, R.; Miller, A. Acinetobacter baumannii OmpA Is a Selective Antibiotic Permeant Porin. ACS Infect. Dis. 2018, 4, 373–381.
  62. Smani, Y.; Fàbrega, A.; Roca, I.; Sánchez-Encinales, V.; Vila, J.; Pachón, J. Role of OmpA in the multidrug resistance phenotype of Acinetobacter baumannii. Antimicrob. Agents Chemother. 2014, 58, 1806–1808.
  63. Tiku, V.; Kofoed, E.M.; Yan, D.; Kang, J.; Xu, M.; Reichelt, M.; Dikic, I.; Tan, M.W. Outer membrane vesicles containing OmpA induce mitochondrial fragmentation to promote pathogenesis of Acinetobacter baumannii. Sci. Rep. 2021, 11, 618.
  64. Kim, S.W.; Choi, C.H.; Moon, D.C.; Jin, J.S.; Lee, J.H.; Shin, J.H.; Kim, J.M.; Lee, Y.C.; Seol, S.Y.; Cho, D.T.; et al. Serum resistance of Acinetobacter baumannii through the binding of factor H to outer membrane proteins. FEMS Microbiol. Lett. 2009, 301, 224–231.
  65. Choi, C.H.; Lee, J.S.; Lee, Y.C.; Park, T.I.; Lee, J.C. Acinetobacter baumannii invades epithelial cells and outer membrane protein A mediates interactions with epithelial cells. BMC Microbiol. 2008, 8, 216.
  66. An, Z.; Huang, X.; Zheng, C.; Ding, W. Acinetobacter baumannii outer membrane protein A induces HeLa cell autophagy via MAPK/JNK signaling pathway. Int. J. Med. Microbiol. IJMM 2019, 309, 97–107.
  67. Choi, C.H.; Lee, E.Y.; Lee, Y.C.; Park, T.I.; Kim, H.J.; Hyun, S.H.; Kim, S.A.; Lee, S.K.; Lee, J.C. Outer membrane protein 38 of Acinetobacter baumannii localizes to the mitochondria and induces apoptosis of epithelial cells. Cell. Microbiol. 2005, 7, 1127–1138.
  68. Mussi, M.A.; Relling, V.M.; Limansky, A.S.; Viale, A.M. CarO, an Acinetobacter baumannii outer membrane protein involved in carbapenem resistance, is essential for L-ornithine uptake. FEBS Lett. 2007, 581, 5573–5578.
  69. Siroy, A.; Molle, V.; Lemaître-Guillier, C.; Vallenet, D.; Pestel-Caron, M.; Cozzone, A.J.; Jouenne, T.; Dé, E. Channel formation by CarO, the carbapenem resistance-associated outer membrane protein of Acinetobacter baumannii. Antimicrob. Agents Chemother. 2005, 49, 4876–4883.
  70. Fernández-Cuenca, F.; Smani, Y.; Gómez-Sánchez, M.C.; Docobo-Pérez, F.; Caballero-Moyano, F.J.; Domínguez-Herrera, J.; Pascual, A.; Pachón, J. Attenuated virulence of a slow-growing pandrug-resistant Acinetobacter baumannii is associated with decreased expression of genes encoding the porins CarO and OprD-like. Int. J. Antimicrob. Agents 2011, 38, 548–549.
  71. Smani, Y.; Dominguez-Herrera, J.; Pachón, J. Association of the outer membrane protein Omp33 with fitness and virulence of Acinetobacter baumannii. J. Infect. Dis. 2013, 208, 1561–1570.
  72. Rumbo, C.; Tomás, M.; Fernández Moreira, E.; Soares, N.C.; Carvajal, M.; Santillana, E.; Beceiro, A.; Romero, A.; Bou, G. The Acinetobacter baumannii Omp33-36 porin is a virulence factor that induces apoptosis and modulates autophagy in human cells. Infect. Immun. 2014, 82, 4666–4680.
  73. Smani, Y.; Pachón, J. Loss of the OprD homologue protein in Acinetobacter baumannii: Impact on carbapenem susceptibility. Antimicrob. Agents Chemother. 2013, 57, 677.
  74. Dupont, M.; Pagès, J.M.; Lafitte, D.; Siroy, A.; Bollet, C. Identification of an OprD homologue in Acinetobacter baumannii. J. Proteome Res. 2005, 4, 2386–2390.
  75. Catel-Ferreira, M.; Nehmé, R.; Molle, V.; Aranda, J.; Bouffartigues, E.; Chevalier, S.; Bou, G.; Jouenne, T.; Dé, E. Deciphering the function of the outer membrane protein OprD homologue of Acinetobacter baumannii. Antimicrob. Agents Chemother. 2012, 56, 3826–3832.
  76. Smani, Y.; Docobo-Pérez, F.; López-Rojas, R.; Domínguez-Herrera, J.; Ibáñez-Martínez, J.; Pachón, J. Platelet-activating factor receptor initiates contact of Acinetobacter baumannii expressing phosphorylcholine with host cells. J. Biol. Chem. 2012, 287, 26901–26910.
  77. Catel-Ferreira, M.; Marti, S.; Guillon, L.; Jara, L.; Coadou, G.; Molle, V.; Bouffartigues, E.; Bou, G.; Shalk, I.; Jouenne, T.; et al. The outer membrane porin OmpW of Acinetobacter baumannii is involved in iron uptake and colistin binding. FEBS Lett. 2016, 590, 224–231.
  78. Sheldon, J.R.; Skaar, E.P. Acinetobacter baumannii can use multiple siderophores for iron acquisition, but only acinetobactin is required for virulence. PLoS Pathog. 2020, 16, e1008995.
  79. Daniel, C.; Haentjens, S.; Bissinger, M.C.; Courcol, R.J. Characterization of the Acinetobacter baumannii Fur regulator: Cloning and sequencing of the fur homolog gene. FEMS Microbiol. Lett. 1999, 170, 199–209.
  80. Fiester, S.E.; Arivett, B.A.; Schmidt, R.E.; Beckett, A.C.; Ticak, T.; Carrier, M.V.; Ghosh, R.; Ohneck, E.J.; Metz, M.L.; Sellin Jeffries, M.K.; et al. Iron-Regulated Phospholipase C Activity Contributes to the Cytolytic Activity and Virulence of Acinetobacter baumannii. PLoS ONE 2016, 11, e0167068.
  81. Stahl, J.; Bergmann, H.; Göttig, S.; Ebersberger, I.; Averhoff, B. Acinetobacter baumannii Virulence Is Mediated by the Concerted Action of Three Phospholipases D. PLoS ONE 2015, 10, e0138360.
  82. Geissdörfer, W.; Kok, R.G.; Ratajczak, A.; Hellingwerf, K.J.; Hillen, W. The genes rubA and rubB for alkane degradation in Acinetobacter sp. strain ADP1 are in an operon with estB, encoding an esterase, and oxyR. J. Bacteriol. 1999, 181, 4292–4298.
  83. Li, H.; Wang, Q.; Wang, R.; Zhang, Y.; Wang, X.; Wang, H. Global regulator SoxR is a negative regulator of efflux pump gene expression and affects antibiotic resistance and fitness in Acinetobacter baumannii. Medicine 2017, 96, e7188.
  84. Hood, M.I.; Mortensen, B.L.; Moore, J.L.; Zhang, Y.; Kehl-Fie, T.E.; Sugitani, N.; Chazin, W.J.; Caprioli, R.M.; Skaar, E.P. Identification of an Acinetobacter baumannii zinc acquisition system that facilitates resistance to calprotectin-mediated zinc sequestration. PLoS Pathog. 2012, 8, e1003068.
  85. Nairn, B.L.; Lonergan, Z.R.; Wang, J.; Braymer, J.J.; Zhang, Y.; Calcutt, M.W.; Lisher, J.P.; Gilston, B.A.; Chazin, W.J.; de Crécy-Lagard, V.; et al. The Response of Acinetobacter baumannii to Zinc Starvation. Cell Host Microbe 2016, 19, 826–836.
  86. Juttukonda, L.J.; Chazin, W.J.; Skaar, E.P. Acinetobacter baumannii Coordinates Urea Metabolism with Metal Import To Resist Host-Mediated Metal Limitation. mBio 2016, 7.
  87. Rosenberg, H.; Gerdes, R.G.; Chegwidden, K. Two systems for the uptake of phosphate in Escherichia coli. J. Bacteriol. 1977, 131, 505–511.
  88. Gil-Marqués, M.L.; Labrador Herrera, G.; Miró Canturri, A.; Pachón, J.; Smani, Y.; Pachón-Ibáñez, M.E. Role of PstS in the Pathogenesis of Acinetobacter baumannii Under Microaerobiosis and Normoxia. J. Infect. Dis. 2020, 222, 1204–1212.
  89. Ahmad, S.; Raza, S.; Uddin, R.; Azam, S.S. Comparative subtractive proteomics based ranking for antibiotic targets against the dirtiest superbug: Acinetobacter baumannii. J. Mol. Graph. Model. 2018, 82, 74–92.
  90. Johnson, T.L.; Waack, U.; Smith, S.; Mobley, H.; Sandkvist, M. Acinetobacter baumannii Is Dependent on the Type II Secretion System and Its Substrate LipA for Lipid Utilization and In Vivo Fitness. J. Bacteriol. 2015, 198, 711–719.
  91. Liu, C.-C.; Kuo, H.-Y.; Tang, C.Y.; Chang, K.-C.; Liou, M.-L. Prevalence and mapping of a plasmid encoding a type IV secretion system in Acinetobacter baumannii. Genomics 2014, 104, 215–223.
  92. Pérez, A.; Merino, M.; Rumbo-Feal, S.; Álvarez-Fraga, L.; Vallejo, J.A.; Beceiro, A.; Ohneck, E.J.; Mateos, J.; Fernández-Puente, P.; Actis, L.A.; et al. The FhaB/FhaC two-partner secretion system is involved in adhesion of Acinetobacter baumannii AbH12O-A2 strain. Virulence 2017, 8, 959–974.
  93. Roussin, M.; Rabarioelina, S.; Cluzeau, L.; Cayron, J.; Lesterlin, C.; Salcedo, S.P.; Bigot, S. Identification of a Contact-Dependent Growth Inhibition (CDI) System That Reduces Biofilm Formation and Host Cell Adhesion of Acinetobacter baumannii DSM30011 Strain. Front. Microbiol. 2019, 10, 2450.
  94. Bentancor, L.V.; Camacho-Peiro, A.; Bozkurt-Guzel, C.; Pier, G.B.; Maira-Litrán, T. Identification of Ata, a multifunctional trimeric autotransporter of Acinetobacter baumannii. J. Bacteriol. 2012, 194, 3950–3960.
  95. Lopez, J.; Ly, P.M.; Feldman, M.F. The Tip of the VgrG Spike Is Essential to Functional Type VI Secretion System Assembly in Acinetobacter baumannii. mBio 2020, 11.
  96. Jin, J.S.; Kwon, S.O.; Moon, D.C.; Gurung, M.; Lee, J.H.; Kim, S.I.; Lee, J.C. Acinetobacter baumannii secretes cytotoxic outer membrane protein A via outer membrane vesicles. PLoS ONE 2011, 6, e17027.
  97. Espinal, P.; Marti, S.; Vila, J. Effect of biofilm formation on the survival of Acinetobacter baumannii on dry surfaces. J. Hosp. Infect. 2012, 80, 56–60.
  98. Tipton, K.A.; Chin, C.-Y.; Farokhyfar, M.; Weiss, D.S.; Rather, P.N. Role of capsule in resistance to disinfectants, host antimicrobials, and desiccation in Acinetobacter baumannii. Antimicrob. Agents Chemother. 2018, 62.
  99. Geisinger, E.; Isberg, R.R. Antibiotic modulation of capsular exopolysaccharide and virulence in Acinetobacter baumannii. PLoS Pathog. 2015, 11, e1004691.
  100. Zeidler, S.; Müller, V. Coping with low water activities and osmotic stress in Acinetobacter baumannii: Significance, current status and perspectives. Environ. Microbiol. 2019, 21, 2212–2230.
  101. Boll, J.M.; Tucker, A.T.; Klein, D.R.; Beltran, A.M.; Brodbelt, J.S.; Davies, B.W.; Trent, M.S. Reinforcing Lipid A Acylation on the Cell Surface of Acinetobacter baumannii Promotes Cationic Antimicrobial Peptide Resistance and Desiccation Survival. mBio 2015, 6, e00478-15.
  102. Behzadi, P. Classical chaperone-usher (CU) adhesive fimbriome: Uropathogenic Escherichia coli (UPEC) and urinary tract infections (UTIs). Folia Microbiol. 2020, 65, 45–65.
  103. Allen, J.L.; Tomlinson, B.R.; Casella, L.G.; Shaw, L.N. Regulatory networks important for survival of Acinetobacter baumannii within the host. Curr. Opin. Microbiol. 2020, 55, 74–80.
  104. Colquhoun, J.M.; Rather, P.N. Insights Into Mechanisms of Biofilm Formation in Acinetobacter baumannii and Implications for Uropathogenesis. Front. Cell. Infect. Microbiol. 2020, 10, 253.
  105. Ahmad, I.; Nygren, E.; Khalid, F.; Myint, S.L.; Uhlin, B.E. A Cyclic-di-GMP signalling network regulates biofilm formation and surface associated motility of Acinetobacter baumannii 17978. Sci. Rep. 2020, 10, 1991.
  106. Bertrand, C.; Thibessard, A.; Bruand, C.; Lecointe, F.; Leblond, P. Bacterial NHEJ: A never ending story. Mol. Microbiol. 2019, 111, 1139–1151.
  107. Norton, M.D.; Spilkia, A.J.; Godoy, V.G. Antibiotic resistance acquired through a DNA damage-inducible response in Acinetobacter baumannii. J. Bacteriol. 2013, 195, 1335–1345.
  108. Hassan, K.A.; Liu, Q.; Henderson, P.J.; Paulsen, I.T. Homologs of the Acinetobacter baumannii AceI transporter represent a new family of bacterial multidrug efflux systems. mBio 2015, 6, e01982-14.
  109. Abdi, S.N.; Ghotaslou, R.; Ganbarov, K.; Mobed, A.; Tanomand, A.; Yousefi, M.; Asgharzadeh, M.; Kafil, H.S. Acinetobacter baumannii Efflux Pumps and Antibiotic Resistance. Infect. Drug Resist. 2020, 13, 423–434.
  110. Liu, Q.; Hassan, K.A.; Ashwood, H.E.; Gamage, H.; Li, L.; Mabbutt, B.C.; Paulsen, I.T. Regulation of the aceI multidrug efflux pump gene in Acinetobacter baumannii. J. Antimicrob. Chemother. 2018, 73, 1492–1500.
  111. Juttukonda, L.J.; Green, E.R.; Lonergan, Z.R.; Heffern, M.C.; Chang, C.J.; Skaar, E.P. Acinetobacter baumannii OxyR Regulates the Transcriptional Response to Hydrogen Peroxide. Infect. Immun. 2019, 87, e00413-18.
  112. Wang, X.; Cole, C.G.; DuPai, C.D.; Davies, B.W. Protein Aggregation is Associated with Acinetobacter baumannii Desiccation Tolerance. Microorganisms 2020, 8, 343.
  113. Cardoso, K.; Gandra, R.F.; Wisniewski, E.S.; Osaku, C.A.; Kadowaki, M.K.; Felipach-Neto, V.; Haus, L.F.A.; Simão, R.C.G. DnaK and GroEL are induced in response to antibiotic and heat shock in Acinetobacter baumannii. J. Med. Microbiol. 2010, 59 Pt 9, 1061–1068.
  114. Nwugo, C.C.; Gaddy, J.A.; Zimbler, D.L.; Actis, L.A. Deciphering the iron response in Acinetobacter baumannii: A proteomics approach. J. Proteom. 2011, 74, 44–58.
  115. Ramos, J.L.; Gallegos, M.T.; Marqués, S.; Ramos-González, M.I.; Espinosa-Urgel, M.; Segura, A. Responses of Gram-negative bacteria to certain environmental stressors. Curr. Opin. Microbiol. 2001, 4, 166–171.
  116. Stacy, D.M.; Welsh, M.A.; Rather, P.N.; Blackwell, H.E. Attenuation of quorum sensing in the pathogen Acinetobacter baumannii using non-native N-Acyl homoserine lactones. ACS Chem. Biol. 2012, 7, 1719–1728.
  117. Bhargava, N.; Sharma, P.; Capalash, N. Quorum sensing in Acinetobacter: An emerging pathogen. Crit. Rev. Microbiol. 2010, 36, 349–360.
  118. Zarrilli, R. Acinetobacter baumannii virulence determinants involved in biofilm growth and adherence to host epithelial cells. Virulence 2016, 7, 367–368.
  119. Saipriya, K.; Swathi, C.H.; Ratnakar, K.S.; Sritharan, V. Quorum-sensing system in Acinetobacter baumannii: A potential target for new drug development. J. Appl. Microbiol. 2020, 128, 15–27.
  120. Modarresi, F.; Azizi, O.; Shakibaie, M.R.; Motamedifar, M.; Mosadegh, E.; Mansouri, S. Iron limitation enhances acyl homoserine lactone (AHL) production and biofilm formation in clinical isolates of Acinetobacter baumannii. Virulence 2015, 6, 152–161.
  121. Piepenbrink, K.H.; Lillehoj, E.; Harding, C.M.; Labonte, J.W.; Zuo, X.; Rapp, C.A.; Munson, R.S.; Goldblum, S.E., Jr.; Feldman, M.F.; Gray, J.J.; et al. Structural Diversity in the Type IV Pili of Multidrug-resistant Acinetobacter. J. Biol. Chem. 2016, 291, 22924–22935.
  122. Nie, D.; Hu, Y.; Chen, Z.; Li, M.; Hou, Z.; Luo, X.; Mao, X.; Xue, X. Outer membrane protein A (OmpA) as a potential therapeutic target for Acinetobacter baumannii infection. J. Biomed. Sci. 2020, 27, 26.
  123. Park, J.S.; Lee, W.C.; Yeo, K.J.; Ryu, K.S.; Kumarasiri, M.; Hesek, D.; Lee, M.; Mobashery, S.; Song, J.H.; Kim, S.I.; et al. Mechanism of anchoring of OmpA protein to the cell wall peptidoglycan of the gram-negative bacterial outer membrane. FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol. 2012, 26, 219–228.
  124. Viale, A.M.; Evans, B.A. Microevolution in the major outer membrane protein OmpA of Acinetobacter baumannii. Microb. Genom. 2020, 6, e000381.
  125. Oh, K.W.; Kim, K.; Islam, M.M.; Jung, H.W.; Lim, D.; Lee, J.C.; Shin, M. Transcriptional Regulation of the Outer Membrane Protein A in Acinetobacter baumannii. Microorganisms 2020, 8, 706.
  126. Kuo, H.Y.; Chao, H.H.; Liao, P.C.; Hsu, L.; Chang, K.C.; Tung, C.H.; Chen, C.H.; Liou, M.L. Functional Characterization of Acinetobacter baumannii Lacking the RNA Chaperone Hfq. Front. Microbiol. 2017, 8, 2068.
  127. Limansky, A.S.; Mussi, M.A.; Viale, A.M. Loss of a 29-kilodalton outer membrane protein in Acinetobacter baumannii is associated with imipenem resistance. J. Clin. Microbiol. 2002, 40, 4776–4778.
  128. Wu, X.; Chavez, J.D.; Schweppe, D.K.; Zheng, C.; Weisbrod, C.R.; Eng, J.K.; Murali, A.; Lee, S.A.; Ramage, E.; Gallagher, L.A.; et al. In vivo protein interaction network analysis reveals porin-localized antibiotic inactivation in Acinetobacter baumannii strain AB5075. Nat. Commun. 2016, 7, 13414.
  129. Zahn, M.; Bhamidimarri, S.P.; Baslé, A.; Winterhalter, M.; van den Berg, B. Structural Insights into Outer Membrane Permeability of Acinetobacter baumannii. Structure 2016, 24, 221–231.
  130. Huang, W.; Wang, S.; Yao, Y.; Xia, Y.; Yang, X.; Long, Q.; Sun, W.; Liu, C.; Li, Y.; Ma, Y. OmpW is a potential target for eliciting protective immunity against Acinetobacter baumannii infections. Vaccine 2015, 33, 4479–4485.
  131. Sarshar, M.; Scribano, D.; Ambrosi, C.; Palamara, A.T.; Masotti, A. Fecal microRNAs as Innovative Biomarkers of Intestinal Diseases and Effective Players in Host-Microbiome Interactions. Cancers 2020, 12, 2174.
  132. Ahmadi Badi, S.; Moshiri, A.; Fateh, A.; Rahimi Jamnani, F.; Sarshar, M.; Vaziri, F.; Siadat, S.D. Microbiota-Derived Extracellular Vesicles as New Systemic Regulators. Front. Microbiol. 2017, 8, 1610.
  133. Eijkelkamp, B.A.; Hassan, K.A.; Paulsen, I.T.; Brown, M.H. Investigation of the human pathogen Acinetobacter baumannii under iron limiting conditions. BMC Genom. 2011, 12, 126.
  134. He, X.; Lu, F.; Yuan, F.; Jiang, D.; Zhao, P.; Zhu, J.; Cheng, H.; Cao, J.; Lu, G. Biofilm formation caused by clinical Acinetobacter baumannii isolates is associated with overexpression of the AdeFGH efflux pump. Antimicrob. Agents Chemother. 2015, 59, 4817–4825.
  135. Ajiboye, T.; Skiebe, E.; Wilharm, G. Contributions of ferric uptake regulator Fur to the sensitivity and oxidative response of Acinetobacter baumannii to antibiotics. Microb. Pathog. 2018, 119, 35–41.
  136. Kröger, C.; Kary, S.C.; Schauer, K.; Cameron, A.D. Genetic regulation of virulence and antibiotic resistance in Acinetobacter baumannii. Genes 2017, 8, 12.
  137. Hesse, L.E.; Lonergan, Z.R.; Beavers, W.N.; Skaar, E.P. The Acinetobacter baumannii Znu System Overcomes Host-Imposed Nutrient Zinc Limitation. Infect. Immun. 2019, 87, e00746-19.
  138. Green, E.R.; Juttukonda, L.J.; Skaar, E.P. The Manganese-Responsive Transcriptional Regulator MumR Protects Acinetobacter baumannii from Oxidative Stress. Infect. Immun. 2020, 88, e00762-19.
  139. Chekabab, S.M.; Harel, J.; Dozois, C.M. Interplay between genetic regulation of phosphate homeostasis and bacterial virulence. Virulence 2014, 5, 786–793.
  140. Skerniškytė, J.; Karazijaitė, E.; Deschamps, J.; Krasauskas, R.; Armalytė, J.; Briandet, R.; Sužiedėlienė, E. Blp1 protein shows virulence-associated features and elicits protective immunity to Acinetobacter baumannii infection. BMC Microbiol. 2019, 19, 259.
  141. Korotkov, K.V.; Sandkvist, M.; Hol, W.G. The type II secretion system: Biogenesis, molecular architecture and mechanism. Nat. Rev. Microbiol. 2012, 10, 336–351.
  142. Harding, C.M.; Kinsella, R.L.; Palmer, L.D.; Skaar, E.P.; Feldman, M.F. Medically relevant Acinetobacter species require a type II secretion system and specific membrane-associated chaperones for the export of multiple substrates and full virulence. PLoS Pathog. 2016, 12, e1005391.
  143. Smith, C.A.; Antunes, N.T.; Stewart, N.K.; Toth, M.; Kumarasiri, M.; Chang, M.; Mobashery, S.; Vakulenko, S.B. Structural basis for carbapenemase activity of the OXA-23 β-lactamase from Acinetobacter baumannii. Chem. Biol. 2013, 20, 1107–1115.
  144. Leo, J.C.; Grin, I.; Linke, D. Type V secretion: Mechanism (s) of autotransport through the bacterial outer membrane. Philos. Trans. R. Soc. B Biol. Sci. 2012, 367, 1088–1101.
  145. Fan, E.; Chauhan, N.; Udatha, D.; Leo, J.C.; Linke, D. Type V Secretion Systems in Bacteria. Microbiol. Spectr. 2016, 4, 305–335.
  146. Hood, R.D.; Peterson, S.B.; Mougous, J.D. From Striking Out to Striking Gold: Discovering that Type VI Secretion Targets Bacteria. Cell Host Microbe 2017, 21, 286–289.
  147. Lewis, J.M.; Deveson Lucas, D.; Harper, M.; Boyce, J.D. Systematic Identification and Analysis of Acinetobacter baumannii Type VI Secretion System Effector and Immunity Components. Front. Microbiol. 2019, 10, 2440.
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Cecilia Ambrosi
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