Prokaryotic Amyloids in Interspecies Interactions: History
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Subjects: Microbiology
Contributor:
Anastasiia O. Kosolapova
,
Kirill S. Antonets
,
Mikhail V. Belousov
,
Anton A. Nizhnikov

Amyloids are fibrillar protein aggregates with an ordered spatial structure called “cross-β”. While some amyloids are associated with development of approximately 50 incurable diseases of humans and animals, the others perform various crucial physiological functions. The greatest diversity of amyloids functions is identified within prokaryotic species where they, being the components of the biofilm matrix, function as adhesins, regulate the activity of toxins and virulence factors, and compose extracellular protein layers. Amyloid state is widely used by different pathogenic bacterial species in their interactions with eukaryotic organisms. These amyloids, being functional for bacteria that produce them, are associated with various bacterial infections in humans and animals. Thus, the repertoire of the disease-associated amyloids includes not only dozens of pathological amyloids of mammalian origin but also numerous microbial amyloids. Although the ability of symbiotic microorganisms to produce amyloids has recently been demonstrated, functional roles of prokaryotic amyloids in host–symbiont interactions as well as in the interspecies interactions within the prokaryotic communities remain poorly studied. Here, we summarize the current findings in the field of prokaryotic amyloids, classify different interspecies interactions where these amyloids are involved, and hypothesize about their real occurrence in nature as well as their roles in pathogenesis and symbiosis.

  • amyloid
  • bacteria
  • interspecies interactions
  • host–pathogen
  • host–symbiont
  • microbial community
  • outer membrane protein
  • biofilm
  • Omp
  • toxin

1. Introduction

The term “amyloid” dates back to the previous century. In 1838, Matthias Schleiden introduced “amyloid” (from Latin “amylum”—starch) to describe a starch material in plant cells [1]. In 1854, Rudolf Virchow first used “amyloid” to characterize cerebral inclusions that colored blue in a reaction with iodine [2]. Based on the iodine test reaction, Virchow hypothesized about polysaccharide nature of pathological inclusions in so-called “waxy” human organs that underwent irreversible changes called amyloidosis [1]. Five years later, in 1859, August Kekulé and Carl Friedreich showed that the inclusions in “waxy” spleen were enriched in nitrogen and were rather proteinaceous than starchy [3].

Currently, the term “amyloid” refers to the highly ordered protein aggregates formed by unbranched fibrils the protein monomers of which are stacked by intermolecular β-sheets [4] composed of β-strands running perpendicular to the fibril axis and connected via hydrogen bonds [5]. The spatial organization of amyloid fibrils determines “cross-β” diffraction pattern characterized by two scattering diffraction signals: ~4.7 Å, corresponding to the interstrand distance, and ~10 Å, corresponding to the distance between β-sheets [6][7]. This structure is typical of amyloids, yet there is no rule without exception: phenol-soluble modulin α3 (PSMα3), a secreted protein of Staphylococcus aureus, forms fibrils possessing physicochemical properties of amyloids but shows “cross-α” diffraction pattern that corresponds to perpendicularly stacked α-helices rather than to β-sheets in “cross-β” structure [8].

Unique physicochemical properties of amyloid fibrils allow discriminating amyloids from the non-amyloid protein aggregates. Two defining features of amyloids are: (i) their ability to form mainly unbranched fibrils that can be shown with electron or atomic force microscopy [9][10]; and (ii) their “cross-β” structure, which can be directly demonstrated by X-ray diffraction (XRD) [6] or solid state nuclear magnetic resonance (SS-NMR) [11]. Circular dichroism spectroscopy (CD), often used to evaluate the enrichment of protein aggregates in β-sheets, cannot prove their “cross-β” structure [12]. Amyloids are resistant to treatment with ionic detergents such as sodium dodecyl sulfate (SDS) [13] and proteases [14], although these properties vary significantly depending on the amyloids themselves and the proteins from which they are formed [15][16]. Amyloids also bind specific dyes [17], which was demonstrated for the first time in 1922 with Congo red (CR) dye [18]. Further, amyloids have been shown to exhibit “apple-green” birefringence in polarized light upon CR binding [19] and demonstrate specific fluorescence emission spectra [20]. Another widely used dye for the analysis of amyloids is Thioflavin T (ThT), which binding to amyloids leads to an increased fluorescence intensity [21].

For more than 150 years, amyloid studies were mainly focused on their roles in the development of incurable diseases in humans and animals, such as Alzheimer’s disease and various localized and systemic amyloidoses. Despite extensive study, the molecular mechanisms of amyloid toxicity remain unclear. To date, two dominant hypotheses have been proposed [22]. Amyloid hypothesis suggests that deposition of amyloid fibrils themselves causes toxicity leading to cell death [23]. The second hypothesis postulates that soluble oligomers rather than fibrillar polymers cause the main cytotoxic effect [24]. Both hypotheses are unable to fully explain observed data. Thus, there are new currently emerging hypotheses. In particular, lipid-chaperone hypothesis is based on the observation that toxicity of amyloidogenic proteins is associated with their ability to damage cell membranes and suggests that phospholipids can act as molecular chaperones promoting interaction of amyloidogenic proteins with cell membranes [22][25].

The paradigm describing amyloid as harmful agents shifted with the discovery of functional amyloids that can perform various physiological roles [26][27]. To date, functional amyloids have been identified within all three domains of life, Archaea, Bacteria, and Eukarya, and their current number is approximately equal or even exceeds the number of pathogenic ones [27][28]. The greatest diversity of functional amyloids is identified within prokaryotic organisms. Since the discovery of amyloid properties of the curli fimbriae of Escherichia coli [29], more than 30 amyloidogenic proteins of Bacteria and Archaea have been identified. Part of them form amyloid fibrils under the native conditions and act as functional amyloids involved in the interspecies interactions with their hosts or within microbial communities. The variety of the prokaryotic amyloid-forming proteins, the methods that have been used to analyze their amyloid properties in vitro and in vivo, and their functions in the amyloid and soluble states are summarized in Table 1. In this paper, we review the published scientific data on the diversity of prokaryotic amyloids and discuss their biological functions with regard to their role in different types of interspecies interactions in both pathogenic and symbiotic aspects.

Table 1. Amyloidogenic proteins of prokaryotes, their properties, functions, and involvement in the interspecies interactions.

Species

Protein

Function of Soluble Protein

Function of Amyloid

Amyloid Properties *

Type of Inter-Species Interactions Mediated by Amyloid **

References

In Vitro

In Vivo

Domain: Bacteria

Phylum: Proteobacteria

Escherichia coli,
Salmonella enterica

CsgA (curli),
AgfA (tafi)

No data

Biofilm matrix protein; surface adhesion; intercellular adhesion

CR (Congo red) absorbance, ThT (Thioflavin T) fluorescence, CD (Circular dichroism), FTIR (Fourier-transform infrared spectroscopy), XDR (X-ray diffraction)

Extracellular fibrils formation

I

[29][30][31][32]

Pseudomonas aeruginosa,
P. fluorescens,
P. putida

FapC

No data

Biofilm matrix protein; facilitates mechanical stiffness; enhances hydrophobic properties; binds quorum-sensing signal molecules

TEM (Transmission electron microscopy), FTIR, XDR

Extracellular fibrils formation; purified native fibrils: CD, FTIR, ThT fluorescence

I

[33][34][35]

Legionella pneumophila

Not identified

No data

Biofilm matrix protein

No data

ThT fluorescence, CR staining and WO1 antibodies binding of extracellular polymer matrix of biofilm

I

[36]

Escherichia coli

OmpA

Outer membrane porin

Virulence factor; amyloid function is unknown

ThT fluorescence, TEM, CD (for N-terminal domain)

No data

I ***

[37]

Escherichia coli

OmpC

Outer membrane porin

Virulence factor; amyloid function is unknown

Proteinase K resistance, TEM, ThT fluorescence, CR absorbance and birefringence

No data

I ***

[38]

Mannheimia haemolytica

OmpP2-like protein

Outer membrane porin

Biofilm matrix protein; adhesion to host’s tissues

CR binding

Fibrils on the cell surface, binding anti-OmpP2-like protein antibodies

I

[39]

Rhizobium leguminosarum

RopA

Outer membrane porin

Component of extracellular capsule

CD, CR birefringence, ThT fluorescence, TEM, detergent-resistance, trypsin resistance

SDS (Sodium dodecyl sulfate)-resistant  polymer formation, fibrils on the cell surface, binding anti-RopA antibodies

III ***

[40]

Rhizobium leguminosarum

RopB

No data

Component of extracellular capsule

CD, CR birefringence, ThT fluorescence, TEM, detergent-resistance, trypsin and pepsin resistance

SDS-resistant polymer formation, fibrils on the cell surface, binding anti-RopB antibodies

III ***

[40]

Klebsiella pneumoniae

Microcin Е492

Pore-forming toxin

Toxin inactivation

TEM, CD, ThT fluorescence, CR absorbance, proteinase K resistance, XDR

Fibril formation on the surface of Microcin E492 secreting strain (TEM)

II

[41][42]

Xanthomonas axonopodis

HpaG (harpin)

No data

Virulence factor; induces plant hypersensitive response

TEM, CD, CR absorbance and birefringence, proteinase K resistance

No data

I ***

[43]

Pseudomonas syringae

HrpZ (harpin)

No data

Virulence factor; induces plant hypersensitive response

TEM

No data

I ***

[43]

Erwinia amylovora

HrpN (harpin)

No data

Virulence factor; induces plant hypersensitive response

TEM

No data

I ***

[43]

Gallibacterium anatis

EF-Tu

Elongation factor

Biofilm matrix protein; surface adhesion

TEM

TEM, CR binding, antibodies against curli

N/a

[44]

Phylum: Firmicutes

Bacillus subtilis,
Bacillus cereus

TasA

No data

Biofilm matrix protein; facilitates biofilm integrity; binds exopolysaccharides on the initial steps of multispecies biofilm formation

TEM, CD, NMR (Nuclear magnetic resonance), FTIR

Anti-TasA antibodies binding extracellular fibrils in biofilm matrix; native fibrils: TEM, CR absorbance, ThT fluorescence

I, II

[45][46][47]

Staphylococcus aureus

PSMs

No data

Biofilm matrix protein

TEM, ThT fluorescence, NMR (cross-α structure)

Extracellular fibrils in biofilm matrix while Δabpsm mutant were unable to form fibrils

I

[8][48]

Staphylococcus aureus

SuhB

No data

Biofilm matrix protein; intercellular adhesion

CR absorbance, ThT fluorescence, FTIR, SEM, XDR

No data

I ***

[49]

Staphylococcus aureus

AgrD

Propeptide; autoinducing peptide pheromone (AIP) precursor

N-terminal peptide, cleaved during AIP maturation, forms amyloid; biofilm matrix component

N-terminal domain: ThT fluorescence, TEM, CR absorbance, CD

Fibrils formed by N-terminal domain of AgrD in biofilm matrix

I

[50]

Staphylococcus aureus

Bap

No data

Surface adhesion; intercellular adhesion; promotes biofilm formation in acidic conditions

Bap B-domain: ThT fluorescence, CR absorbance, TEM, FTIR, CD

Anti-Bap antibodies binding fibrils formation on the cell surface

I

[51]

Enterococcus faecalis

cOB1

Pheromone; part of the pheromone-based conjugation system

Prevention of conjugation; initiate the aggregation of biofilm matrix proteins (such as Esp)

ThT fluorescence, CR absorbance, CD, TEM

No data

II ***

[52]

Enterococcus faecalis

Esp

No data

Biofilm matrix protein

C-DAG assay: CR binding, TEM;
N-terminal domain: SEM (Scanning electron microscopy), FTIR, CD, CR absorbance, ThT fluorescence;
Fibril formation on the surface of Δbap S. aureus expressing Esp_N

No data

I ***

[53]

Staphylococcus epidermidis

Aap

Intercellular adhesion

Biofilm matrix protein

ThT fluorescence, CR absorbance, TEM, CD

SDS-resistant aggregates, binding anti-Aap antibodies, were extracted from biofilm-forming bacteria

I

[54]

Staphylococcus epidermidis

Sbp

No data

Scaffolding protein in biofilms

TEM, AFM, FTIR, CR absorbance, ThT fluoerescence

ThS-binding inclusions, expressing Sbp

I

[55]

Streptococcus mutans

Adhesin P1

No data

Biofilm matrix protein; adhesion to tooth surface

CR birefringence, ThT fluorescence, TEM, XDR

No data

I ***

[56]

Streptococcus mutans

WapA

No data

Biofilm matrix protein

CR birefringence, ThT fluorescence, TEM, XDR

No data

I ***

[57][58]

Streptococcus mutans

Smu_63c

No data

Biofilm matrix protein

CR birefringence, ThT fluorescence, TEM, XDR

No data

I ***

[57][58]

Bacillus subtilis

HelD

Helicase

Amyloid function is unknown

CD, ThT fluorescence, CR absorbance, XDR

ThS-binding inclusions in strain, overexpressing HelD

N/a

[59]

Clostridium botulinum

Rho****

Transcription terminator

Modulates transcription; causes genome-wide changes in transcriptome

Analysis of prion-like domain:
ThT, ThS and CR fluorescence,
FTIR, TEM; C-DAG (Curli-dependent amyloid generator) assay: CR birefringence, SDS-resistance

SDS-stable aggregate formation in E. coli

N/a

[60][61]

Solibacillus silvestris

Bioemulsifier BE-AM1

No data

Cell surface properties modulation; biofilm matrix protein

CR birefringence, FTIR, CD, TEM

No data

N/a

[62][63]

Listeria monocytogenes

Listeriolysin O

Toxin, that forms pores in phagolysosome’s membrane

Toxin inactivation

CD, TEM, CR fluorescence and absorbance, ThT fluorescence, trypsin resistance

No data

I

[64]

Phylum: Actinobacteria

Streptomyces coelicolor

ChpA-H (chaplin)

No data

Lowering of the surface tension; assists aerial hyphae formation

CD, TEM, XDR, FTIR

Native extracts: ThT fluorescence, TEM, CD

N/a

[65][66]

Streptomyces coelicolor

RdlB (rodlin)

No data

Rodlet layer formation; assists aerial hyphae formation

ThT fluorescence, TEM, CD, XDR

No data

N/a

[67]

Mycobacterium tuberculosis

CarD

Transcription factor

Amyloid function is unknown

ThT fluorescence, TEM, SDS-resistance, CD (increase in β-sheet content during heating)

ThS-binding (Thioflavin S) inclusions in strain, overexpressing CarD

N/a

[68]

Mycobacterium tuberculosis

MTP

No data

Adhesion to host’s tissues

TEM, CR binding

TEM, SDS resistance of fibrils

I ***

[69]

Domain: Archaea
Phylum: Euryarchaeota

Haloferax volcanii

Not identified

No data

Biofilm matrix protein

No data

Fluorescence of biofilms stained with CR and ThT

N/a

[70]

Methanosaeta thermophila

MspA

No data

Tubular sheaths component; facilitates its stiffness

TEM, ThT, CD, FTIR, XDR

Intact sheaths: TEM, WO1 antibodies;
purified sheaths: TEM, WO1 antibodies, ThT, FTIR, XDR

N/a

[71]

Methanospirillum hungatei

MspA

No data

Tubular sheaths component; facilitates its stiffness

No data

Intact sheaths: WO1 antibodies;
purified sheaths: TEM, FTIR

N/a

[72]

* CR, Congo red; ThT, Thioflavin T; ThS, Thioflavin S; C-DAG, Curli-dependent amyloid generator; CD, Circular dichroism; FTIR, Fourier-transform infrared spectroscopy; XDR, X-ray diffraction; NMR, Nuclear magnetic resonance; SDS, Sodium dodecyl sulfate; SEM, Scanning electron microscopy; TEM, Transmission electron microscopy. ** Type of proven or hypothetical inter-species interactions: Type I, host–pathogen interactions; Type II, interactions between different microbial species in the communities; Type III, host–symbiont interactions; N/a, not applicable. *** Hypothetical interaction based on the structural protein function. **** This protein also possesses infectious prion properties [60].

2. Amyloids of Biofilms and Their Involvement in Host–Pathogen Interactions and Interspecies Interactions within Prokaryotic Communities

The highest number of the identified functional amyloids of prokaryotes is represented by the biofilm components. Biofilm is a community of microorganisms encapsulated in hydrated extracellular polymeric substances (EPS) [73]. EPS account for almost 90% of the dry weight of a biofilm and include polysaccharides, eDNA, lipids, and proteins [73]. The biofilm proteins include the extracellular enzymes, carrying out degradation and remodulation of EPS, and structural proteins, providing stability and integrity to biofilm [74]. The stability of amyloid fibrils, originating from their spatial structure, makes them perfect structural proteins of the biofilm EPS. Thus, amyloids, making the biofilms stable, serve as scaffolding proteins, as well as play a role in surface and intercellular adhesion [75]. At the same time, a biofilm formation is linked with the development of 65% of all bacterial infections and 80% of chronic bacterial infections [76] such as periodontitis, chronic rhinosinusitis, chronic otitis media, chronic urinary tract infections, and cystic fibrosis pneumonia [77]. Biofilm formation creates a local microenvironment (such as anaerobic conditions or zones with lowered pH), to protect the microbial community from the antibiotic treatment, host defense, and environmental stresses [78] and contributes to formation of so-called “persister” microbial sub-population formed by dormant, multi-drug resistant cells [79]. Thus, amyloids that have been identified within the pathogenic bacteria and being part and parcel of the biofilm matrix can act as virulence and pathogenesis factors [80].

The curli are the main structural proteins of EPS of Escherichia coli biofilms [29][31][81], adhering to both biotic and abiotic surfaces [82][83][84]. In 2002, amyloid properties were demonstrated for E. coli curlin CsgA [29] and in 2007 for Salmonella enterica curlin AgfA [31]. Curli amyloid formation involves secretion system Type VIII and is controlled by the expression of two operons—csgABC and csgDEFG (curli-specific genes)—in E. coli [29]. CsgA is the main structural protein while CsgB nucleates CsgA polymerization on the cell surface [85]. CsgC, the third gene from csgABC operon, is a periplasmic chaperone that prevents a premature CsgA polymerization [86]. Lipoprotein CsgG forms a pore in the outer membrane of bacterial cells and mediates the transport of the curli subunits to the cell surface [87]. CsgE and CsgF proteins facilitate CsgA and CsgB transport through CsgG pore [88]. CsgE interacts directly with the pore and secreted proteins and acts as a secretion adaptor [88]. The precise function of CsgF remains unclear, but it is required for the normal functioning of the CsgB nucleator [88][89].

Despite curli fimbriae were initially characterized within clinical isolates, the precise role of amyloid formation of those proteins in infection remained unclear [90][91]. Indeed, curli operons are not only present in the genomes of pathogenic strains of Proteobacteria but are also widespread within the non-pathogenic strains [92]; and curli homologs have also been found within Firmicutes, Thermodesulfobacteria, and Bacteroidetes phyla [92], including Porphyromonas gingivalis [93].

The curli fimbriae apparently take part in bacteria’s adhesion to host cells [94], interact with the host proteins [95][96], and trigger the host immune response [97] during an infection. The curli-producing E. coli and Salmonella spp. strains are highly adhesive to a variety of cell lines. Thus, curli-producing K-12 E. coli has demonstrated a higher level of adherence to human uroepithelial cells in comparison to curli deficient strains [94]. Similarly, higher levels of curli production in S. typhimurium SR-11 are linked to adherence to a murine small intestinal epithelial [98]. Nevertheless, ΔcsgA strain of enteroaggregative E. coli (EAEC) has not shown any decrease in adherence to mammalian cells, suggesting that the E. coli system of adhesion to host cells includes not only the curli fimbriae but a broad repertoire of molecular factors [99]. Moreover, curli expression levels have been significantly lowered within the enterohemorrhagic E. coli [100][101] and invasive Salmonella spp. strains [102].

The curli interact with the host proteins including fibronectin, laminin, and plasminogen [90][103][104]. They also interact with Toll-like receptors, which leads to an innate immune system activation [105][106]. On the contrary, the curli can protect bacterial cells from the immune reactions via antimicrobial peptides sequestering [107] and inhibition of the classical pathway of the complement cascade activation [108].

The Gram-negative bacterium Pseudomonas aeruginosa is a cause of nosocomial and chronic infections associated with the biofilm formation, for example during cystic fibrosis pneumonia [109]. The biofilm matrix of Pseudomonas species includes amyloid fibrils formed by Fap proteins [33]. Amyloid fibril formation in Pseudomonas is controlled by a fapABCDEF operon, evolutionally distant from the curli system of E. coli [33]. Unlike the curli system, fap genes are unique for Proteobacteria species [110]. FapC is the main structural component of amyloid fibrils, whereas FapB, similar to CsgB from curlin system, acts as a nucleator of fibril polymerization [34]. Transport of FapB and FapC subunits to the cell surface is facilitated by FapF protein which forms trimer pores in the outer membrane of bacteria [111].

Fap amyloid fibrils increase the biofilm hydrophobicity, facilitate mechanical stiffness [112], and reversibly bind quorum sensing molecules, supporting their role as a reservoir for signal molecules that can modulate the reaction of the microbial community to turbulent environmental conditions [35]. Similar to curli, Fap proteins contribute to bacterial adhesion to a substrate. Thus, Pseudomonas strains overexpressing fap operon have a highly adhesive phenotype and an enhanced ability to form biofilms [33][34]. However, overexpression of fap operon notably changes the complete proteomic landscape, thus it is impossible to assume the direct connection between Fap amyloidogenesis and the altered phenotype [113]. The role of Fap proteins in Pseudomonas virulence has been demonstrated using P. aureginosa mutant strain with fapC deletion. Strains with fapC deletion had lowered virulence to Caenorhabditis elegans [114]. In murine models of acute and chronic infections, fap operon transcription in P. aureginosa was also significantly elevated [115].

Gram-positive bacterium Bacillus subtilis forms biofilms on the surface of solid agar plates and floating biofilms, or pellicles, at the air–liquid interface [116]. TasA protein, the main component of Bacillus biofilm EPS [117], can form amyloids both in vitro and in vivo [45][46][47]. While B. subtilis is a soil-dwelling non-pathogenic bacterium, Bacillus cereus is a soil bacterium responsible for the development of food-borne disease. However, the role of biofilm formation and TasA amyloid formation in a particular disease development is unclear. At the same time, TasA amyloids of Bacillus apparently contribute to the interspecies interaction in complex biofilm communities as TasA amyloid fibrils adhere to Streptococcus mutans exopolysaccharides during the initial steps of multispecies biofilm formation [118].

Biofilms are the main form for Streptococcus mutans—a Gram-positive bacterium involved in the dental plaques and cavities formation [119][120]. Within the proteins of S. mutans amyloid formation in biofilm, EPS has been demonstrated for adhesin P1, WapA, and Smu_63c proteins [56][57]. Adhesin P1 and WapA protein represent substrates of sortase—an enzyme cleaving the C-terminal signal motif of proteins and attaching them to the cell wall through transpeptidase reaction [121]. As a result of adhesin P1 and WapA protein cleavage amyloid-forming fragments, C123 and AgA, respectively, are generated [57]. Smu_63c is a secreted protein that forms amyloids under acid conditions. These amyloids act as negative regulators of genetic competence and biofilm cell density [57]. The deletion of one of the genes encoding amyloid-forming proteins was shown not to affect the ability of S. mutans to form biofilms. At the same time, double (lacking in adhesin P1 and WapA) or triple deletions lead to decreased biofilm formation [57]. Mutants lacking in the adhesin P1 gene have a lowered virulence in the murine cavity models, but the precise role of adhesin P1 amyloidogenesis in virulence is still unclear [122].

Similar to P. aeruginosa, Staphylococcus species, S. aureus and S. epidermidis, are the leading causes of nosocomial infections [123]. At the same time, S. aureus as well as S. epidermidis can act not only as pathogens but as a part of the normal skin microbiome. Staphylococcus biofilm formation promotes adhesion and substrate colonization, including multicellular host tissues, as well as contributes to protection against antibiotic agents and immune system elements [124]. Thus, the biochemical content of Staphylococcus biofilms is a target of extensive research. The extracellular polymeric substances of staphylococcal biofilms include a variety of amyloid proteins, but their role in host–pathogen interactions have not yet been elucidated.

Sbp and Aap are amyloid-forming proteins of Staphylococcus epidermidis [54][55]. Sbp is a small (18 kDa) extracellular protein that forms the biofilm scaffolds [125]. The amyloid properties of Sbp have been demonstrated in vitro and in E. coli cells [55]. Aap is a multidomain protein associated with the bacterial cell wall. Aap includes the N-terminal region of tandem A-repeats, L-type lectin domain, the region of tandem B-repeats, the proline/glycine-enriched domain, and the C-terminal sortase recognition motif [126]. The ability to form amyloids was demonstrated in vitro for the B-repeats domain. Amyloid formation by B-repeats domain of Aap has a Zn2+-dependent manner and requires metal ions for assembly. The peptides identified as B-repeats and lectin domains of Aap protein were also present in detergent-resistant aggregates from S. epidermidis biofilms [54]. These data are consistent with the research suggesting that Aap protein takes part in biofilm formation in a processed form, lacking the N-terminal domain [127][128]. Sbp and Aap colocalization in biofilms was demonstrated [125] unlike physical interaction in vitro [55].

There is a variety of the identified amyloid-forming proteins composing the extracellular biofilm matrix of Staphylococcus aureus. In 2012, phenol-soluble modulins (PSMs) were identified as a part of fibrils in the biofilm matrix of S. aureus. PSMs also form amyloid fibrils in vitro [48]. In the amyloid state, PSMs stabilize biofilms [48], whereas monomeric PSMs facilitate biofilm detachment [129]. Extracellular DNA (eDNA) is required for PSMs polymerization, so eDNA can act as a nucleator in the amyloid formation [130]. The amyloid properties have been demonstrated for the N-terminal leader peptide of ArgD propeptide (N-ArgD) as well. N-ArgD is a naturally occurring cleavage product of ArgD, appearing due to the AIP (autoinducing peptide) maturation [50] and identified as a part of fibrils, composing the biofilm matrix of S. aureus. The SuhB protein of S. aureus forms amyloids under overexpression in E. coli cells [49]. The precise function of SuhB remains unknown, but the suhB mutant strain is impaired (in terms) of biofilm formation [131]. Another S. aureus protein that can form amyloids extracellularly is called Bap (biofilm-associated protein) [132]. Bap is a multidomain protein anchored to the bacterial cell wall. The N-terminal domain of Bap is cleaved as a result of the Bap processing [133]. The cleaved fragment forms amyloid fibrils in the extracellular space at acidic conditions and low Ca2+ concentration. The Ca2+ concentration increase leads to acquiring a stable globular conformation of the N-terminal domain of Bap [51]. Thus, the N-terminal domain can act not only as a scaffold protein of biofilm but also as a sensor [75]. Local acidosis, the pH decrease, appears in vivo during staphylococcal infection due to glucose utilization by these microorganisms and are accompanied by the host’s inflammatory response [132]. Within S. aureus strains, bap gene has been identified within bovine mastitis isolates [133] but not within human clinical isolates. Deletion in the bap gene leads to a lowered capacity to adhere to the bovine epithelial cells. S. aureus Δbap strain cell titer is also significantly lower at 10 days post-infection [51]. Notably, Esp—the Bap ortholog of Enterococcus faecalis, a commensal bacterium capable of inducing nosocomial infection—forms amyloids, supporting the idea of the prevalence of amyloid formation by Bap-like proteins in biofilm matrix [53].

Pathogenic bacteria can also adhere to the host tissues in a biofilm-independent way. In particular, Mycobacterium tuberculosis possesses adhesive structures called pili. MTP (Mycobacterium tuberculosis pili) are structurally similar to E. coli curli and able to form amyloid fibrils [69]. The mtp gene has been identified only within the pathogenic strains of M. tuberculosis, supporting the key role of MTP in mycobacterial virulence [134]. MTPs bind laminin in vitro while Δmtp strain is unable to bind it [69]. Moreover, mutants show a lowered ability to adhere and invade macrophages and alveolar epithelial cells [135].

Overall, amyloids are widespread structural components of prokaryotic biofilms. Interestingly, not only bacteria but also archaea can contain amyloids in their EPS. For instance, in 2014, the Haloferax volcanii biofilm extracellular matrix was demonstrated to bind ThT and CR dyes with the specific fluorescence [70]. In bacterial biofilms, the amyloids form a scaffold and facilitate their stiffness and integrity. Amyloids may also contribute to intercellular and surface adhesion, which makes them one of the key virulence factors of pathogenic bacteria. Thus, the crucial role of amyloids of biofilms in adhesion is apparently widespread across various prokaryotes, thus allowing us to suppose that there are numerous still unknown biofilm-associated amyloids underlying the pathogenesis and development of infectious diseases. Considering that the number of only human pathogenic bacteria species is about 1500 [136] and 65% of them form biofilms in disease-associated processes [55], the real number of such prokaryotic amyloids involved in pathogenesis in humans and animals could exceed hundreds and even thousands. The interactions between bacteria in microbial communities represent another type of interspecies interactions where the bacterial biofilm amyloids are involved by providing the cell adhesion to heterogeneous exopolysaccharides and where the number of yet unidentified prokaryotic amyloids could be remarkably high.

This entry is adapted from the peer-reviewed paper 10.3390/ijms21197240

References

  1. Kyle, R.A. Amyloidosis: A convoluted story. J. Haematol. 2001, 114, 529–538, doi:10.1046/j.1365-2141.2001.02999.x.
  2. Virchow, R. Ueber eine im Gehirn und Rückenmark des Menschen aufgefundene Substanz mit der chemischen Reaction der Cellulose. Arch. Pathol. Anat. Physiol. Klin. Med. 1854, 6, 135–138, doi:10.1007/BF01930815.
  3. Sipe, J.D.; Cohen, A.S. Review: History of the amyloid fibril. Struct. Biol. 2000, 130, 88–98, doi:10.1006/jsbi.2000.4221.
  4. Sipe, J.D.; Benson, M.D.; Buxbaum, J.N.; Ikeda, S.; Merlini, G.; Saraiva, M.J.M.; Westermark, P. Amyloid fibril proteins and amyloidosis: Chemical identification and clinical classification International Society of Amyloidosis 2016 Nomenclature Guidelines. Amyloid 2016, 23, 209–213, doi:10.1080/13506129.2016.1257986.
  5. Riek, R.; Eisenberg, D.S. The activities of amyloids from a structural perspective. Nature 2016, 539, 227–235, doi:10.1038/nature20416.
  6. Eanes, E.D.; Glenner, G.G. X-ray diffraction studies on amyloid filaments. Histochem. Cytochem. 1968, 16, 673–677, doi:10.1177/16.11.673.
  7. Sunde, M.; Serpell, L.C.; Bartlam, M.; Fraser, P.E.; Pepys, M.B.; Blake, C.C. Common core structure of amyloid fibrils by synchrotron X-ray diffraction. Mol. Biol. 1997, 273, 729–739, doi:10.1006/jmbi.1997.1348.
  8. Tayeb-Fligelman, E.; Tabachnikov, O.; Moshe, A.; Goldshmidt-Tran, O.; Sawaya, M.R.; Coquelle, N.; Colletier, J.P.; Landau, M. The cytotoxic Staphylococcus aureus PSMα3 reveals a cross-α amyloid-like fibril. Science 2017, 355, 831–833, doi:10.1126/science.aaf4901.
  9. Shirahama, T.; Cohen, A.S. High-resolution electron microscopic analysis of the amyloid fibril. Cell Biol. 1967, 33, 679–708, doi:10.1083/jcb.33.3.679.
  10. Adamcik, J.; Mezzenga, R. Study of amyloid fibrils via atomic force microscopy. Opin. Colloid Interface Sci. 2012, 17, 369–376, doi:10.1016/j.cocis.2012.08.001.
  11. Tycko, R.; Ishii, Y. Constraints on supramolecular structure in amyloid fibrils from two-dimensional solid-state NMR spectroscopy with uniform isotopic labeling. Am. Chem. Soc. 2003, 125, 6606–6607, doi:10.1021/ja0342042.
  12. Greenfield, N.J. Using circular dichroism spectra to estimate protein secondary structure. Protoc. 2006, 1, 2876–2890, doi:10.1038/nprot.2006.202.
  13. Selkoe, D.J.; Ihara, Y.; Salazar, F.J. Alzheimer’s disease: Insolubility of partially purified paired helical filaments in sodium dodecyl sulfate and urea. Science 1982, 215, 1243–1245, doi:10.1126/science.6120571.
  14. Bolton, D.C.; McKinley, M.P.; Prusiner, S.B. Identification of a protein that purifies with the scrapie prion. Science 1982, 218, 1309–1311, doi:10.1126/science.6815801.
  15. Zurdo, J.; Guijarro, J.I.; Dobson, C.M. Preparation and characterization of purified amyloid fibrils. Am. Chem. Soc. 2001, 123, 8141–8142, doi:10.1021/ja016229b.
  16. Nizhnikov, A.A.; Alexandrov, A.I.; Ryzhova, T.A.; Mitkevich, O.V.; Dergalev, A.A.; Ter-Avanesyan, M.D.; Galkin, A.P. Proteomic screening for amyloid proteins. PLoS ONE 2014, 9, e116003, doi:10.1371/journal.pone.0116003.
  17. Sipe, J.D.; Benson, M.D.; Buxbaum, J.N.; Ikeda, S.; Merlini, G.; Saraiva, M.J.M.; Westermark, P. Nomenclature 2014: Amyloid fibril proteins and clinical classification of the amyloidosis. Amyloid 2014, 21, 221–224, doi:10.3109/13506129.2014.964858.
  18. Bennhold, H. Specific staining of amyloid by Congo red (in German). Med. Wochenschr. 1922, 69, 1537–1538. Available online: https://archive.org/details/munchenermedizin6921unse/page/1536/mode/2up (Accessed on 30 September 2020).
  19. Divry, P.; Florkin, M. Sur les propriétés optiques de l’amyloïde, C.R. Biol. 1927, 97, 1808–1810.
  20. Kan, A.; Birnbaum, D.P.; Praveschotinunt, P.; Joshi, N.S. Congo red fluorescence for rapid in situ characterization of synthetic curli systems. Environ. Microbiol. 2019, 85, e00434-19, doi:10.1128/AEM.00434-19.
  21. Naiki, H.; Higuchi, K.; Hosokawa, M.; Takeda, T. Fluorometric determination of amyloid fibrils in vitro using the fluorescent dye, thioflavine T. Biochem. 1989, 177, 244–249, doi:10.1016/0003-2697(89)90046-8.
  22. Scollo, F.; La Rosa, C. Amyloidogenic Intrinsically Disordered Proteins: New Insights into Their Self-Assembly and Their Interaction with Membranes. Life 2020, 10, 144, doi:10.3390/life10080144.
  23. Chiti, F.; Dobson, C.M. Protein misfolding, functional amyloid, and human disease. Rev. Biochem. 2006, 75, 333–366, doi:10.1146/annurev.biochem.75.101304.123901.
  24. Hebda, J.A.; Miranker, A.D. The interplay of catalysis and toxicity by amyloid intermediates on lipid bilayers: Insights from type II diabetes. Rev. Biophys. 2009, 38, 125–152, doi:10.1146/annurev.biophys.050708.133622.
  25. Sciacca, M.F.M.; Lolicato, F.; Tempra, C.; Scollo, F.; Sahoo, B.R.; Watson, M.D.; García-Viñuales, S.; Milardi, D.; Raudino, A.; Lee, J.C.; et al. The Lipid-Chaperon Hypothesis: A Common Molecular Mechanism of Membrane Disruption by Intrinsically Disordered Proteins. ChemRxiv 2020, doi:10.26434/chemrxiv.12770504.v1.
  26. Fowler, D.M.; Koulov, A.V.; Balch, W.E.; Kelly, J.W. Functional amyloid—from bacteria to humans. Trends Biochem. Sci. 2007, 32, 217–224, doi:10.1016/j.tibs.2007.03.003.
  27. Nizhnikov, A.A.; Antonets, K.S.; Inge-Vechtomov, S.G. Amyloids: From pathogenesis to function. Biochemistry (Mosc.) 2015, 80, 1127–1144, doi:10.1134/S0006297915090047.
  28. Otzen, D.; Riek, R. Functional amyloids. Cold Spring Harb. Perspect. Biol. 2019, 11, a033860, doi:10.1101/cshperspect.a033860.
  29. Chapman, M.R.; Robinson, L.S.; Pinkner, J.S.; Roth, R.; Heuser, J.; Hammar, M.; Normark, S.; Hultgren, S.J. Role of Escherichia coli curli operons in directing amyloid fiber formation. Science 2002, 295, 851–855, doi:10.1126/science.1067484.
  30. Shewmaker, F.; McGlinchey, R.P.; Thurber, K.R.; McPhie, P.; Dyda, F.; Tycko, R.; Wickner, R.B. The functional curli amyloid is not based on in-register parallel β-sheet structure. Biol. Chem. 2009, 284, 25065–25076, doi:10.1074/jbc.M109.007054.
  31. Gibson, D.L.; White, A.P.; Rajotte, C.M.; Kay, W.W. AgfC and AgfE facilitate extracellular thin aggregative fimbriae synthesis in Salmonella Enteritidis. Microbiology 2007, 153, 1131–1140, doi:10.1099/mic.0.2006/000935-0.
  32. Dueholm, M.S.; Nielsen, S.B.; Hein, K.L.; Nissen, P.; Chapman, M.; Christiansen, G.; Nielsen, P.H.; Otzen, D.E. Fibrillation of the major curli subunit CsgA under a wide range of conditions implies a robust design of aggregation. Biochemistry 2011, 50, 8281–8290, doi:10.1021/bi200967c.
  33. Dueholm, M.S.; Petersen, S.V.; Sønderkær, M.; Larsen, P.; Christiansen, G.; Hein, K.L.; Enghild, J.J.; Nielsen, J.L.; Nielsen, K.L.; Nielsen, P.H.; et al. Functional amyloid in Pseudomonas. Microbiol. 2010, 77, 1009–1020, doi:10.1111/j.1365-2958.2010.07269.x.
  34. Dueholm, M.S.; Søndergaard, M.T.; Nilsson, M.; Christiansen, G.; Stensballe, A.; Overgaard, M.T.; Givskov, M.; Tolker-Nielsen, T.; Otzen, D.E.; Nielsen, P.H. Expression of Fap amyloids in Pseudomonas aeruginosa, fluorescens, and P. putida results in aggregation and increased biofilm formation. Microbiologyopen 2013, 2, 365–382, doi:10.1002/mbo3.81.
  35. Seviour, T.; Hansen, S.H.; Yang, L.; Yau, Y.H.; Wang, V.B.; Stenvang, M.R.; Christiansen, G.; Marsili, E.; Givskov, M.; Chen, Y.; et al. Functional amyloids keep quorum-sensing molecules in check. Biol. Chem. 2015, 290, 6457–6469, doi:10.1074/jbc.M114.613810.
  36. Peterson, C.P.; Sauer, C.; Chatfield, C.H. The Extracellular Polymeric Substances of Legionella pneumophila Biofilms Contain Amyloid Structures. Microbiol. 2018, 75, 736–744, doi:10.1007/s00284-018-1440-1.
  37. Danoff, E.J.; Fleming, K.G.; Aqueous, Unfolded OmpA forms amyloid-like fibrils upon self-association. PLoS ONE 2015, 10, e0132301, doi:10.1371/journal.pone.0132301.
  38. Rajan, J.J.S.; Santiago, T.C.; Singaravel, R.; Ignacimuthu, S. Outer membrane protein C (OmpC) of Escherichia coli induces neurodegeneration in mice by acting as an amyloid. Lett. 2016, 38, 689–700, doi:10.1007/s10529-015-2025-8.
  39. García, J.F.M.; Vaca, S.; Delgado, N.L.; Uribe-García, A.; Vázquez, C.; Alonso, P.S.; Cortes, J.X.; Cordoba, A.C.; Abascal, E.N. Mannheimia haemolytica OmpP2-like is an amyloid-like protein, forms filaments, takes part in cell adhesion and is part of biofilms. Antonie Van Leeuwenhoek 2018, 111, 2311–2321, doi:10.1007/s10482-018-1122-9.
  40. Kosolapova, A.O.; Belousov, M.V.; Sulatskaya, A.I.; Belousova, M.E.; Sulatsky, M.I.; Antonets, K.S.; Volkov, K.V.; Lykholay, A.N.; Shtark, O.Y.; Vasileva, E.N.; et al. Two novel amyloid proteins, RopA and RopB, from the root nodule bacterium Rhizobium leguminosarum. Biomolecules 2019, 9, 694, doi:10.3390/biom9110694.
  41. Bieler, S.; Estrada, L.; Lagos, R.; Baeza, M.; Castilla, J.; Soto, C. Amyloid formation modulates the biological activity of a bacterial protein. Biol. Chem. 2005, 280, 26880–26885, doi:10.1074/jbc.M502031200.
  42. Arranz, R.; Mercado, G.; Martín-Benito, J.; Giraldo, R.; Monasterio, O.; Lagos, R.; Valpuesta, J.M. Structural characterization of microcin E492 amyloid formation: Identification of the precursors. Struct. Biol. 2012, 178, 54–60, doi:10.1016/j.jsb.2012.02.015.
  43. Oh, J.; Kim, J.-G.; Jeon, E.; Yoo, C.-H.; Moon, J.S.; Rhee, S.; Hwang, I. Amyloidogenesis of type III-dependent harpins from plant pathogenic bacteria. Biol. Chem. 2007, 282, 13601–13609, doi:10.1074/jbc.M602576200.
  44. López-Ochoa, J.; Montes-García, J.F.; Vázquez, C.; Sánchez-Alonso, P.; Pérez-Márquez, V.M.; Blackall, P.J.; Vaca, S.; Negrete-Abascal, E. Gallibacterium elongation factor-Tu possesses amyloid-like protein characteristics, participates in cell adhesion, and is present in biofilms. Microbiol. 2017, 55, 745–752, doi:10.1007/s12275-017-7077-0.
  45. Romero, D.; Aguilar, C.; Losick, R.; Kolter, R. Amyloid fibers provide structural integrity to Bacillus subtilis Proc. Natl. Acad. Sci. USA 2010, 107, 2230–2234, doi:10.1073/pnas.0910560107.
  46. El Mammeri, N.; Hierrezuelo, J.; Tolchard, J.; Cámara-Almirón, J.; Caro-Astorga, J.; Álvarez-Mena, A.; Dutour, A.; Berbon, M.; Shenoy, J.; Morvan, E.; et al. Molecular architecture of bacterial amyloids in Bacillus FASEB J. 2019, 33, 12146–12163, doi:10.1096/fj.201900831R.
  47. Sarang, M.C.; Nerurkar, A.S. Amyloid protein produced by cereus CR4 possesses bioflocculant activity and has potential application in microalgae harvest. Biotechnol. Lett. 2020, 42, 79–91, doi:10.1007/s10529-019-02758-3.
  48. Schwartz, K.; Syed, A.K.; Stephenson, R.E.; Rickard, A.H.; Boles, B.R. Functional amyloids composed of phenol soluble modulins stabilize Staphylococcus aureus PLoS Pathog. 2012, 8, e1002744, doi:10.1371/journal.ppat.1002744.
  49. Dutta, A.; Bhattacharyya, S.; Kundu, A.; Dutta, D.; Das, A.K. Macroscopic amyloid fiber formation by staphylococcal biofilm associated SuhB protein. Chem. 2016, 217, 32–41, doi:10.1016/j.bpc.2016.07.006.
  50. Schwartz, K.; Sekedat, M.D.; Syed, A.K.; O’Hara, B.; Payne, D.E.; Lamb, A.; Boles, B.R. The AgrD N-terminal leader peptide of Staphylococcus aureus has cytolytic and amyloidogenic properties. Immun. 2014, 82, 3837–3844, doi:10.1128/IAI.02111-14.
  51. Taglialegna, A.; Navarro, S.; Ventura, S.; Garnett, J.A.; Matthews, S.; Penades, J.R.; Lasa, I.; Valle, J. Staphylococcal Bap Proteins Build Amyloid Scaffold Biofilm Matrices in Response to Environmental Signals. PLoS Pathog. 2016, 12, e1005711, doi:10.1371/journal.ppat.1005711.
  52. Gour, S.; Kumar, V.; Rana, M.; Yadav, J.K. Pheromone peptide cOB1 from native Enterococcus faecalis forms amyloid-like structures: A new paradigm for peptide pheromones. Pept. Sci. 2019, 25, e3178, doi:10.1002/psc.3178.
  53. Taglialegna, A.; Matilla-Cuenca, L.; Dorado-Morales, P.; Navarro, S.; Ventura, S.; Garnett, J.A.; Lasa, I.; Valle, J. The biofilm-associated surface protein Esp of Enterococcus faecalis forms amyloid-like fibers. NPJ Biofilms Microbiomes 2020, 6, 15, doi:10.1038/s41522-020-0125-2.
  54. Yarawsky, A.E.; Johns, S.L.; Schuck, P.; Herr, A.B. The biofilm adhesion protein Aap from Staphylococcus epidermidis forms zinc-dependent amyloid fibers. Biol. Chem. 2020, 295, 4411–4427, doi:10.1074/jbc.RA119.010874.
  55. Wang, Y.; Jiang, J.; Gao, Y.; Sun, Y.; Dai, J.; Wu, Y.; Qu, D.; Ma, G.; Fang, X. Staphylococcus epidermidis small basic protein (Sbp) forms amyloid fibrils, consistent with its function as a scaffolding protein in biofilms. Biol. Chem. 2018, 293, 14296–14311, doi:10.1074/jbc.RA118.002448.
  56. Oli, M.W.; Otoo, H.N.; Crowley, P.J.; Heim, K.P.; Nascimento, M.M.; Ramsook, C.B.; Lipke, P.N.; Brady, L.J. Functional amyloid formation by Streptococcus mutans. Microbiology 2012, 158, 2903–2916, doi:10.1099/mic.0.060855-0.
  57. Besingi, R.N.; Wenderska, I.B.; Senadheera, D.B.; Cvitkovitch, D.G.; Long, J.R.; Wen, Z.T.; Brady, L.J. Functional amyloids in streptococcus mutans, their use as targets of biofilm inhibition and initial characterization of SMU_63c. Microbiology 2017, 163, 488–501, doi:10.1099/mic.0.000443.
  58. Barran-Berdon, A.L.; Ocampo, S.; Haider, M.; Morales-Aparicio, J.; Ottenberg, G.; Kendall, A.; Yarmola, E.; Mishra, S.; Long, J.R.; Hagen, S.J.; et al. Enhanced purification coupled with biophysical analyses shows cross-β structure as a core building block for Streptococcus mutans functional amyloids. Rep. 2020, 10, 5138, doi:10.1038/s41598-020-62115-7.
  59. Kaur, G.; Kapoor, S.; Thakur, K.G. Bacillus subtilis HelD, an RNA Polymerase Interacting Helicase, Forms Amyloid-Like Fibrils. Microbiol. 2018, 9, 1934, doi:10.3389/fmicb.2018.01934.
  60. Yuan, A.H.; Hochschild, A. A bacterial global regulator forms a prion. Science 2017, 355, 198–201, doi:10.1126/science.aai7776.
  61. Pallarès, I.; Iglesias, V.; Ventura, S. The rho termination factor of Clostridium botulinum contains a prion-like domain with a highly amyloidogenic core. Microbiol. 2016, 6, 1516, doi:10.3389/fmicb.2015.01516.
  62. Markande, A.R.; Acharya, S.R.; Nerurkar, A.S. Physicochemical characterization of a thermostable glycoprotein bioemulsifier from Solibacillus silvestris Process Biochem. 2013, 48, 1800–1808, doi:10.1016/j.procbio.2013.08.017.
  63. Markande, A.R.; Nerurkar, A.S. Bioemulsifier (BE-AM1) produced by Solibacillus silvestris AM1 is a functional amyloid that modulates bacterial cell-surface properties. Biofouling 2016, 32, 1153–1162, doi:10.1080/08927014.2016.1232716.
  64. Bavdek, A.; Kostanjšek, R.; Antonini, V.; Lakey, J.H.; Dalla Serra, M.; Gilbert, R.J.C.; Anderluh, G. PH dependence of listeriolysin O aggregation and pore-forming ability. FEBS J. 2012, 279, 126–141, doi:10.1111/j.1742-4658.2011.08405.x.
  65. Claessen, D.; Rink, R.; de Jong, W.; Siebring, J.; de Vreugd, P.; Boersma, F.G.H.; Dijkhuizen, L.; Wösten, H.A.B. A novel class of secreted hydrophobic proteins is involved in aerial hyphae formation in Streptomyces coelicolor by forming amyloid-like fibrils. Genes Dev. 2003, 17, 1714–1726, doi:10.1101/gad.264303.
  66. Sawyer, E.B.; Claessen, D.; Haas, M.; Hurgobin, B.; Gras, S.L. The assembly of individual chaplin peptides from Streptomyces coelicolor into functional amyloid fibrils. PLoS ONE 2011, 6, e18839, doi:10.1371/journal.pone.0018839.
  67. Yang, W.; Willemse, J.; Sawyer, E.B.; Lou, F.; Gong, W.; Zhang, H.; Gras, S.L.; Claessen, D.; Perrett, S. The propensity of the bacterial rodlin protein RdlB to form amyloid fibrils determines its function in Streptomyces coelicolor. Rep. 2017, 7, 42867, doi:10.1038/srep42867.
  68. Kaur, G.; Kaundal, S.; Kapoor, S.; Grimes, J.M.; Huiskonen, J.T.; Thakur, K.G. Mycobacterium tuberculosis CarD, an essential global transcriptional regulator forms amyloid-like fibrils. Rep. 2018, 8, 10124, doi:10.1038/s41598-018-28290-4.
  69. Alteri, C.J.; Xicohtencatl-Cortes, J.; Hess, S.; Caballero-Olin, G.; Giron, J.A.; Friedman, R.L.; Xicohténcatl-Cortes, J.; Hess, S.; Caballero-Olin, G.; Girón, J.A.; et al. Mycobacterium tuberculosis produces pili during human infection. Natl. Acad. Sci. USA 2007, 104, 5145–5150, doi:10.1073/pnas.0602304104.
  70. Chimileski, S.; Franklin, M.J.; Papke, R.T. Biofilms formed by the archaeon Haloferax volcanii exhibit cellular differentiation and social motility, and facilitate horizontal gene transfer. BMC Biol. 2014, 12, 65, doi:10.1186/s12915-014-0065-5.
  71. Dueholm, M.S.; Larsen, P.; Finster, K.; Stenvang, M.R.; Christiansen, G.; Vad, B.S.; Bøggild, A.; Otzen, D.E.; Nielsen, P.H. The tubular sheaths encasing Methanosaeta thermophila filaments are functional amyloids. Biol. Chem. 2015, 290, 20590–20600, doi:10.1074/jbc.M115.654780.
  72. Christensen, L.F.B.; Hansen, L.M.; Finster, K.; Christiansen, G.; Nielsen, P.H.; Otzen, D.E.; Dueholm, M.S. The sheaths of Methanospirillum are made of a new type of amyloid protein. Microbiol. 2018, 9, 2729, doi:10.3389/fmicb.2018.02729.
  73. Flemming, H.C.; Wingender, J. The biofilm matrix. Rev. Microbiol. 2010, 8, 623–633, doi:10.1038/nrmicro2415.
  74. Flemming, H.C.; Neu, T.R.; Wozniak, D.J. The EPS matrix: The “House of Biofilm Cells.” Bacteriol. 2007, 189, 7945–7947, doi:10.1128/JB.00858-07.
  75. Taglialegna, A.; Lasa, I.; Valle, J. Amyloid structures as biofilm matrix scaffolds. Bacteriol. 2016, 198, 2579–2588, doi:10.1128/JB.00122-16.
  76. Jamal, M.; Ahmad, W.; Andleeb, S.; Jalil, F.; Imran, M.; Nawaz, M.A.; Hussain, T.; Ali, M.; Rafiq, M.; Kamil, M.A. Bacterial biofilm and associated infections. Chin. Med. Assoc. 2018, 81, 7–11, doi:10.1016/j.jcma.2017.07.012.
  77. Hall-Stoodley, L.; Stoodley, P. Evolving concepts in biofilm infections. Microbiol. 2009, 11, 1034–1043, doi:10.1111/j.1462-5822.2009.01323.x.
  78. Ciofu, O.; Rojo-Molinero, E.; Macià, M.D.; Oliver, A. Antibiotic treatment of biofilm infections. APMIS 2017, 125, 304–319, doi:10.1111/apm.12673.
  79. Fisher, R.A.; Gollan, B.; Helaine, S. Persistent bacterial infections and persister cells. Rev. Microbiol. 2017, 15, 453–464, doi:10.1038/nrmicro.2017.42.
  80. Van Gerven, N.; Van der Verren, S.E.; Reiter, D.M.; Remaut, H. The role of functional amyloids in bacterial virulence. Mol. Biol. 2018, 430, 3657–3684, doi:10.1016/j.jmb.2018.07.010.
  81. Hung, C.; Zhou, Y.; Pinkner, J.S.; Dodson, K.W.; Crowley, J.R.; Heuser, J.; Chapman, M.R.; Hadjifrangiskou, M.; Henderson, J.P.; Hultgren, S.J. Escherichia coli biofilms have an organized and complex extracellular matrix structure. MBio 2013, 4, e00645-13, doi:10.1128/mBio.00645-13.
  82. Barak, J.D.; Gorski, L.; Naraghi-Arani, P.; Charkowski, A.O. Salmonella enterica virulence genes are required for bacterial attachment to plant tissue. Environ. Microbiol. 2005, 71, 5685–5691, doi:10.1128/AEM.71.10.5685-5691.2005.
  83. Jeter, C.; Matthysse, A.G. Characterization of the binding of diarrheagenic strains of coli to plant surfaces and the role of curli in the interaction of the bacteria with alfalfa sprouts. Mol. Plant-Microbe Interact. 2005, 18, 1235–1242, doi:10.1094/MPMI-18-1235.
  84. Ryu, J.H.; Beuchat, L.R. Biofilm formation by Escherichia coli O157:H7 on stainless steel: Effect of exopolysaccharide and curli production on its resistance to chlorine. Environ. Microbiol. 2005, 71, 247–254, doi:10.1128/AEM.71.1.247-254.2005.
  85. Hammer, N.D.; Schmidt, J.C.; Chapman, M.R. The curli nucleator protein, CsgB, contains an amyloidogenic domain that directs CsgA polymerization. Natl. Acad. Sci. USA 2007, 104, 12494–12499, doi:10.1073/pnas.0703310104.
  86. Evans, M.L.; Chorell, E.; Taylor, J.D.; Åden, J.; Götheson, A.; Li, F.; Koch, M.; Sefer, L.; Matthews, S.J.; Wittung-Stafshede, P.; et al. The bacterial curli system possesses a potent and selective inhibitor of amyloid formation. Cell 2015, 57, 445–455, doi:10.1016/j.molcel.2014.12.025.
  87. Robinson, L.S.; Ashman, E.M.; Hultgren, S.J.; Chapman, M.R. Secretion of curli fibre subunits is mediated by the outer membrane-localized CsgG protein. Microbiol. 2006, 59, 870–881, doi:10.1111/j.1365-2958.2005.04997.x.
  88. Van Gerven, N.; Klein, R.D.; Hultgren, S.J.; Remaut, H. Bacterial amyloid formation: Structural insights into curli biogensis. Trends Microbiol. 2015, 23, 693–706, doi:10.1016/j.tim.2015.07.010.
  89. Nenninger, A.A.; Robinson, L.S.; Hultgren, S.J. Localized and efficient curli nucleation requires the chaperone-like amyloid assembly protein CsgF. Natl. Acad. Sci. USA 2009, 106, 900–905, doi:10.1073/pnas.0812143106.
  90. Olsén, A.; Jonsson, A.; Normark, S. Fibronectin binding mediated by a novel class of surface organelles on Escherichia coli. Nature 1989, 338, 652–655, doi:10.1038/338652a0.
  91. Collinson, S.K.; Clouthier, S.C.; Doran, J.L.; Banser, P.A.; Kay, W.W. Characterization of the agfBA fimbrial operon encoding thin aggregative fimbriae of Salmonella enteritidis. Exp. Med. Biol. 1997, 412, 247–248, doi:10.1007/978-1-4899-1828-4_37.
  92. Dueholm, M.S.; Albertsen, M.; Otzen, D.; Nielsen, P.H. Curli functional amyloid systems are phylogenetically widespread and display large diversity in operon and protein structure. PLoS ONE 2012, 7, e51274, doi:10.1371/journal.pone.0051274.
  93. Shoji, M.; Naito, M.; Yukitake, H.; Sato, K.; Sakai, E.; Ohara, N.; Nakayama, K. The major structural components of two cell surface filaments of Porphyromonas gingivalis are matured through lipoprotein precursors. Microbiol. 2004, 52, 1513–1525, doi:10.1111/j.1365-2958.2004.04105.x.
  94. Kikuchi, T.; Mizunoe, Y.; Takade, A.; Naito, S.; Yoshida, S.I. Curli fibers are required for development of biofilm architecture in Escherichia coli K-12 and enhance bacterial adherence to human uroepithelial cells. Immunol. 2005, 49, 875–884, doi:10.1111/j.1348-0421.2005.tb03678.x.
  95. Olsén, A.; Arnqvist, A.; Hammar, M.; Sukupolvi, S.; Normark, S. The RpoS Sigma factor relieves H-NS-mediated transcriptional repression of csgA, the subunit gene of fibronectin-binding curli in Escherichia coli. Microbiol. 1993, 7, 523–536, doi:10.1111/j.1365-2958.1993.tb01143.x.
  96. Olsén, A.; Wick, M.J.; Mörgelin, M.; Björck, L. Curli, fibrous surface proteins of Escherichia coli, interact with major histocompatibility complex class I molecules. Immun. 1998, 66, 944–949, doi:10.1128/iai.66.3.944-949.1998.
  97. Tükel, Ç.; Raffatellu, M.; Humphries, A.D.; Wilson, R.P.; Andrews-Polymenis, H.L.; Gull, T.; Figueiredo, J.F.; Wong, M.H.; Michelsen, K.S.; Akçelik, M.; et al. CsgA is a pathogen-associated molecular pattern of Salmonella enterica serotype Typhimurium that is recognized by Toll-like receptor 2. Microbiol. 2005, 58, 289–304, doi:10.1111/j.1365-2958.2005.04825.x.
  98. Sukupolvi, S.; Lorenz, R.G.; Gordon, J.I.; Bian, Z.; Pfeifer, J.D.; Normark, S.J.; Rhen, M. Expression of thin aggregative fimbriae promotes interaction of Salmonella typhimurium SR-11 with mouse small intestinal epithelial. Immun. 1997, 65, 5320–5325, doi:10.1128/iai.65.12.5320-5325.1997.
  99. Saldaña, Z.; Xicohtencatl-Cortes, J.; Avelino, F.; Phillips, A.D.; Kaper, J.B.; Puente, J.L.; Girón, J.A. Synergistic role of curli and cellulose in cell adherence and biofilm formation of attaching and effacing Escherichia coli and identification of Fis as a negative regulator of curli. Microbiol. 2009, 11, 992–1006, doi:10.1111/j.1462-2920.2008.01824.x.
  100. Uhlich, G.A.; Keen, J.E.; Elder, R.O. Mutations in the csgD promoter associated with variations in curli expression in certain strains of Escherichia coli O157:H7. Environ. Microbiol. 2001, 67, 2367–2370, doi:10.1128/AEM.67.5.2367-2370.2001.
  101. Uhlich, G.A.; Chen, C.Y.; Cottrell, B.J.; Hofmann, C.S.; Dudley, E.G.; Strobaugh, T.P.; Nguyen, L.H. Phage insertion in mlrA and variations in rpoS limit curli expression and biofilm formation in Escherichia coli serotype O157: H7. Microbiology 2013, 159, 1586–1596, doi:10.1099/mic.0.066118-0.
  102. Gerstel, U.; Römling, U. The csgD promoter, a control unit for biofilm formation in Salmonella typhimurium. Microbiol. 2003, 154, 659–667, doi:10.1016/j.resmic.2003.08.005.
  103. Olsen, A.; Arnqvist, A.; Hammar, M.; Normark, S. Environmental regulation of curli production in Escherichia coli. Agents Dis. 1993, 2, 272–274. PMID: 8173808.
  104. Sjöbring, U.; Pohl, G.; Olsén, A. Plasminogen, absorbed by Escherichia coli expressing curli or by Salmonella enteritidis expressing thin aggregative fimbriae, can be activated by simultaneously captured tissue-type plasminogen activator (t-PA). Microbiol. 1994, 14, 443–452, doi:10.1111/j.1365-2958.1994.tb02179.x.
  105. Rapsinski, G.J.; Wynosky-Dolfi, M.A.; Oppong, G.O.; Tursi, S.A.; Wilson, R.P.; Brodsky, I.E.; Tükel, Ç. Toll-like receptor 2 and NLRP3 cooperate to recognize a functional bacterial amyloid, curli. Immun. 2015, 83, 693–701, doi:10.1128/IAI.02370-14.
  106. Tükel, C.; Wilson, R.P.; Nishimori, J.H.; Pezeshki, M.; Chromy, B.A.; Bäumler, A.J. Responses to amyloids of microbial and host origin are mediated through toll-like receptor 2. Cell Host Microbe 2009, 6, 45–53, doi:10.1016/j.chom.2009.05.020.
  107. Kai-Larsen, Y.; Lüthje, P.; Chromek, M.; Peters, V.; Wang, X.; Holm, Å.; Kádas, L.; Hedlund, K.O.; Johansson, J.; Chapman, M.R.; et al. Uropathogenic Escherichia coli modulates immune responses and its curli fimbriae interact with the antimicrobial peptide LL-37. PLoS Pathog. 2010, 6, e1001010, doi:10.1371/journal.ppat.1001010.
  108. Biesecker, S.G.; Nicastro, L.K.; Paul Wilson, R.; Tükel, Ç. The functional amyloid curli protects escherichia coli against complement-mediated bactericidal activity. Biomolecules 2018, 8, 5, doi:10.3390/biom8010005.
  109. Moradali, M.F.; Ghods, S.; Rehm, B.H.A. Pseudomonas aeruginosa lifestyle: A paradigm for adaptation, survival, and persistence. Cell. Infect. Microbiol. 2017, 7, 39, doi:10.3389/fcimb.2017.00039.
  110. Dueholm, M.S.; Otzen, D.; Nielsen, P.H. Evolutionary insight into the functional amyloids of the pseudomonads. PLoS ONE 2013, 8, e76630, doi:10.1371/journal.pone.0076630.
  111. Rouse, S.L.; Hawthorne, W.J.; Berry, J.L.; Chorev, D.S.; Ionescu, S.A.; Lambert, S.; Stylianou, F.; Ewert, W.; Mackie, U.; Morgan, R.M.L.; et al. A new class of hybrid secretion system is employed in Pseudomonas amyloid biogenesis. Commun. 2017, 8, 263, doi:10.1038/s41467-017-00361-6.
  112. Zeng, G.; Vad, B.S.; Dueholm, M.S.; Christiansen, G.; Nilsson, M.; Tolker-Nielsen, T.; Nielsen, P.H.; Meyer, R.L.; Otzen, D.E. Functional bacterial amyloid increases Pseudomonas biofilm hydrophobicity and stiffness. Microbiol. 2015, 6, 1099, doi:10.3389/fmicb.2015.01099.
  113. Herbst, F.A.; Søndergaard, M.T.; Kjeldal, H.; Stensballe, A.; Nielsen, P.H.; Dueholm, M.S. Major proteomic changes associated with amyloid-induced biofilm formation in Pseudomonas aeruginosa J. Proteome Res. 2015, 14, 72–81, doi:10.1021/pr500938x.
  114. Wiehlmann, L.; Munder, A.; Adams, T.; Juhas, M.; Kolmar, H.; Salunkhe, P.; Tümmler, B. Functional genomics of Pseudomonas aeruginosa to identify habitat-specific determinants of pathogenicity. J. Med. Microbiol. 2007, 297, 615–623, doi:10.1016/j.ijmm.2007.03.014.
  115. Turner, K.H.; Everett, J.; Trivedi, U.; Rumbaugh, K.P.; Whiteley, M. Requirements for Pseudomonas aeruginosa Acute Burn and Chronic Surgical Wound Infection. PLoS Genet. 2014, 10, e1004518, doi:10.1371/journal.pgen.1004518.
  116. Branda, S.S.; González-Pastor, J.E.; Ben-Yehuda, S.; Losick, R.; Kolter, R. Fruiting body formation by Bacillus subtilis. Natl. Acad. Sci. USA 2001, 98, 11621–11626, doi:10.1073/pnas.191384198.
  117. Branda, S.S.; Chu, F.; Kearns, D.B.; Losick, R.; Kolter, R. A major protein component of the Bacillus subtilis biofilm matrix. Microbiol. 2006, 59, 1229–1238, doi:10.1111/j.1365-2958.2005.05020.x.
  118. Duanis-Assaf, D.; Duanis-Assaf, T.; Zeng, G.; Meyer, R.L.; Reches, M.; Steinberg, D.; Shemesh, M. Cell wall associated protein TasA provides an initial binding component to extracellular polysaccharides in dual-species biofilm. Rep. 2018, 8, 9350, doi:10.1038/s41598-018-27548-1.
  119. Hamada, S.; Slade, H.D. Biology, immunology, and cariogenicity of Streptococcus mutans. Rev. 1980, 44, 331–384.
  120. Matsumoto-Nakano, M. Role of Streptococcus mutans surface proteins for biofilm formation. Dent. Sci. Rev. 2018, 54, 22–29, doi:10.1016/j.jdsr.2017.08.002.
  121. Siegel, S.D.; Reardon, M.E.; Ton-That, H. Anchoring of LPXTG-like proteins to the gram-positive cell wall envelope. Top. Microbiol. Immunol. 2017, 404, 159–175, doi:10.1007/82_2016_8.
  122. Crowley, P.J.; Brady, L.J.; Michalek, S.M.; Bleiweis, A.S. Virulence of a spaP mutant of Streptococcus mutans in a gnotobiotic rat model. Immun. 1999, 67, 1201–1206, doi:10.1128/iai.67.3.1201-1206.1999.
  123. Ziebuhr, W. Staphylococcus aureus and Staphylococcus epidermidis: Emerging pathogens in nosocomial infections. Microbiol. 2001, 8, 102–107, doi:10.1159/000060402.
  124. Otto, M. Staphylococcal biofilms. Top Microbiol. Immunol. 2008, 322, 207–228, doi:10.1007/978-3-540-75418-3_10.
  125. Decker, R.; Burdelski, C.; Zobiak, M.; Büttner, H.; Franke, G.; Christner, M.; Saß, K.; Zobiak, B.; Henke, H.A.; Horswill, A.R.; et al. An 18 kDa Scaffold protein is critical for Staphylococcus epidermidis biofilm formation. PLoS Pathog. 2015, 11, e1004735, doi:10.1371/journal.ppat.1004735.
  126. Schaeffer, C.R.; Woods, K.M.; Longo, G.M.; Kiedrowski, M.R.; Paharik, A.E.; Büttner, H.; Christner, M.; Boissy, R.J.; Horswill, A.R.; Rohde, H.; et al. Accumulation-associated protein enhances Staphylococcus epidermidis biofilm formation under dynamic conditions and is required for infection in a rat catheter model. Immun. 2015, 83, 214–226, doi:10.1128/IAI.02177-14.
  127. Rohde, H.; Burdelski, C.; Bartscht, K.; Hussain, M.; Buck, F.; Horstkotte, M.A.; Knobloch, J.K.M.; Heilmann, C.; Herrmann, M.; Mack, D. Induction of Staphylococcus epidermidis biofilm formation via proteolytic processing of the accumulation-associated protein by staphylococcal and host proteases. Microbiol. 2005, 55, 1883–1895, doi:10.1111/j.1365-2958.2005.04515.x.
  128. Paharik, A.E.; Kotasinska, M.; Both, A.; Hoang, T.M.N.; Büttner, H.; Roy, P.; Fey, P.D.; Horswill, A.R.; Rohde, H. The metalloprotease SepA governs processing of accumulation-associated protein and shapes intercellular adhesive surface properties in Staphylococcus epidermidis. Microbiol. 2017, 103, 860–874, doi:10.1111/mmi.13594.
  129. Periasamy, S.; Joo, H.-S.; Duong, A.C.; Bach, T.-H.L.; Tan, V.Y.; Chatterjee, S.S.; Cheung, G.Y.C.; Otto, M. How Staphylococcus aureus biofilms develop their characteristic structure. Natl. Acad. Sci. USA 2012, 109, 1281–1286, doi:10.1073/pnas.1115006109.
  130. Schwartz, K.; Ganesan, M.; Payne, D.E.; Solomon, M.J.; Boles, B.R. Extracellular DNA facilitates the formation of functional amyloids in Staphylococcus aureus Mol. Microbiol. 2015, 99, 123–134, doi:10.1111/mmi.13219.
  131. Boles, B.R.; Thoendel, M.; Roth, A.J.; Horswill, A.R. Identification of genes involved in polysaccharide-independent Staphylococcus aureus biofilm formation. PLoS ONE 2010, 5, e10146, doi:10.1371/journal.pone.0010146.
  132. Di Martino, P. Bap: A new type of functional amyloid. Trends Microbiol. 2016, 24, 682–684, doi:10.1016/j.tim.2016.07.004.
  133. Cucarella, C.; Solano, C.; Valle, J.; Amorena, B.; Lasa, Í.; Penadés, J.R. Bap, a Staphylococcus aureus surface protein involved in biofilm formation. Bacteriol. 2001, 183, 2888–2896, doi:10.1128/JB.183.9.2888-2896.2001.
  134. Naidoo, N.; Ramsugit, S.; Pillay, M. Mycobacterium tuberculosis pili (MTP), a putative biomarker for a tuberculosis diagnostic test. Tuberculosis (Edinb). 2014, 94, 338–345, doi:10.1016/j.tube.2014.03.004.
  135. Ramsugit, S.; Pillay, B.; Pillay, M. Evaluation of the role of Mycobacterium tuberculosis pili (MTP) as an adhesin, invasin, and cytokine inducer of epithelial cells. J. Infect. Dis. 2016, 20, 160–165, doi:10.1016/j.bjid.2015.11.002.
  136. Shaw, L.P.; Wang, A.D.; Dylus, D.; Meier, M.; Pogacnik, G.; Dessimoz, C.; Balloux, F. The phylogenetic range of bacterial and viral pathogens of vertebrates. Mol. Ecol. 2020, doi:10.1111/mec.15463.
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