Plasmid-Mediated mcr Gene-Based Polymyxins: History
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Contributor:
Shakeel Shahzad
,
Mark D. P. Willcox
,
Binod Rayamajhee

The polymyxin antibiotics colistin and polymyxin B have been recently revitalized as bactericidal drugs due to the increase in bacterial resistance to many commonly used antibiotics. Polymyxins were originally derived from the bacterium Paenibacillus polymyxa as the products of fermentation in the form of amphipathic lipopeptide molecules. Polymyxins were discovered in the 1940s to be cyclic lipodecapeptide antibiotics and recognized for therapeutic use in the 1950s. Polymyxins contain conserved components that consist of a d-Phe6-l-Leu7 segment, an N-terminal fatty acyl chain separated by cationic residues (l-α-γ-diaminobutyric acid (Dab)), and segments of the polar amino acid threonine (Thr). Polymyxins target the negatively charged outer membrane lipopolysaccharides (LPSs) of Gram-negative bacteria. Mobilized colistin resistance, mcr, genes are mainly associated with bacterial plasmids. These play an important role in the spread of colistin resistance because of their transferability among different strains in different environments. These mcr genes encode phosphoethanolamine-lipid A transferases that mediate the addition of PEA to the lipid A of an LPS at the 1′ and 4′ positions, causing a significant reduction in the overall negative charge on the bacterial outer membrane. This ultimately leads to the loss of binding affinity of an LPS to the cationic polymyxins and therefore resistance to their action.

  • polymyxin resistance
  • molecular evolution
  • resistance mechanisms
  • mcr

1. Global Dissemination of mcr among Different Bacteria in Different Environments

It is believed that sporadic outbreaks of mcr occurred in Chinese food-producing livestock in 1980 [1]. Since that time, mcr-1-carrying bacterial strains have been reported in several countries among five of the seven continents across the globe [1][2][3][4][5][6] including China [2], India [7], Pakistan [8], Vietnam [9], Laos [10], USA [11], Italy [12], and Japan [13].
The transmission of mcr genes carrying pathogens could occur from animals to humans via direct contact with food animals and pets [14][15][16]. Also, reservoirs for mcr-1-carrying bacteria have been identified in public beaches [17], hospital sewage, wastewater treatment plants [18][19], rivers [16], and water wells in rural areas [20], as well as from houseflies and blowflies [21]. Although data from some studies suggests that flies might be intermediate vectors for transmission of mcr-1-containing bacteria between companion animals and humans [22], the exact route for the spread of mcr-1 and the bacteria carrying mcr-1 needs more thorough investigation.
Several species of Enterobacteriaceae possess mcr-1, such as E. coli where the gene is carried on IncI2 and IncX4 plasmids [23], Enterobacter aerogenes on an IncX4 plasmid [24], E. cloacae on an IncFI plasmid [24], Cronobacter sakazakii on an IncB/O plasmid [25], Citrobacter freundii on an IncHI2 plasmid [26], C. braakii on an IncI2-type plasmid, K. pneumoniae on an IncX4 plasmid [27], Salmonella enterica on IncHI2-like plasmids [28], Shigella sonnei on IncHI2-like plasmids [29], and Raoultella ornithinolytican on an IncHI2 plasmid [30]. Also, mcr-1 variants have been identified in strains co-harboring blaNDM-5 that confers carbapenem resistance to E. coli [8]. The mcr-1.1 gene has been found in the chromosome of E. coli and plasmid p16BU137 of K. pneumoniae from environmental isolates in China [31]. Further details of recently discovered mcr variants and their respective transposons and plasmids are given in Table 1.
Table 1. The evolutionary divergence among mcr variants (mcr-1 to mcr-10) (a score of 1 indicates no divergence between variants; a score of 0 indicates complete divergence).
mcr Gene Number
mcr gene number and source 1 2 3 4 5 6 7 8 9 10
mcr-1 Escherichia coli KU886144.1   0.18 0.67 0.57 0.54 0.22 0.47 0.68 0.71 0.71
mcr-2 Pseudomonas aeruginosa MW811418.1 0.18   0.68 0.58 0.56 0.12 0.49 0.69 0.7 0.72
mcr-3 Escherichia coli MW811424.1 0.67 0.68   0.62 0.75 0.68 0.7 0.76 0.38 0.38
mcr-4 Escherichia coli MW811433.1 0.57 0.58 0.62   0.56 0.58 0.49 0.65 0.65 0.61
mcr-5.1 Salmonella enterica NG055658.1 0.54 0.56 0.75 0.56   0.55 0.43 0.64 0.72 0.73
mcr-6.1 Moraxella sp. NG055781.1 0.22 0.12 0.68 0.58 0.55   0.51 0.72 0.72 0.74
mcr-7 Pseudomonas aeruginosa MW811434.1 0.47 0.49 0.7 0.49 0.43 0.51   0.65 0.71 0.68
mcr-8 Klebsiella pneumoniae MT815555.1 0.68 0.69 0.76 0.65 0.64 0.72 0.65   0.69 0.72
mcr-9 Uncultured bacterium MW478857.1 0.71 0.7 0.38 0.65 0.72 0.72 0.71 0.69   0.22
mcr-10.1 Enterobacter cloacae MN044989.1 0.71 0.72 0.38 0.61 0.73 0.74 0.68 0.72 0.22  
Average evolutionary divergence 0.53 0.52 0.62 0.59 0.61 0.54 0.57 0.69 0.61 0.61
Standard Deviation 0.20 0.23 0.14 0.05 0.11 0.23 0.11 0.04 0.18 0.19
In Australia, colistin resistance was reported among poultry isolates of Aeromonas hydrophila, Alcaligenes faecalis, Myroides odoratus, Hafnia paralvei, and Pseudochrobactrum spp. from a chicken processing unit in the state of Victoria [32]. Furthermore, mcr-1 was found in association with incompatibility group IncI2 plasmids from isolates in the state of New South Wales (NSW) [33], and mcr-1.1 has been detected in E. coli [34]. Similarly, mcr-1.1 and mcr-3 were found among MDR isolates of Salmonella enterica 4 from human and animal sources in NSW [34][35]. An evolutionary analysis of multiple drug-resistant Salmonella enterica serovar 4 indicated that the spread of the mcr-3 variant in lineages 1 and 3 was associated with overseas travel to Southeast Asia [36]. Lineage 1 included mcr-3.1- and blaCTX-M-55-positive isolates of Salmonella enterica sequence type 34 from Europe and Asia that were resistant to colistin and third-generation cephalosporins [36][37]. Whilst mcr-3.2 in lineage 3 was associated with IncHI2 pST3 and IncAC plasmids, wherein the colistin resistance genes were part of dgkA (diacylglycerol kinase) [36][38], which is a small transposable unit associated with IS elements circularized and integrated into Enterobacterales genomes [39].

2. Evolution of mcr Gene Variants from mcr-1 to mcr-10

In the current study, the phylogeny among mcr variants was determined using Molecular Evolutionary Genetics Analysis (MEGA 11) and is shown in Table 1. This shows the pair-end number of substitutions between mcr-1 and mcr-10, with the number of base differences per site indicated. An estimate of evolutionary divergence between the sequences of mcr-1 and mcr-10.1 was performed using MEGA 11. Overall, the average divergence among mcr ranged from 52 ± 20% for mcr-2 compared to all others to 69 ± 4% for mcr-8.
Moreover, phytogenic analysis of mcr-3 also demonstrated that most occurred and evolved among Aeromonas species. This suggested the origin of mcr-3 was Aeromonas species with gradual evolution and transmission of mcr-3 variants to E. coli and K. pneumoniae, while other mcr gradually evolved among E. coli and K. pneumoniae. Interestingly, after the emergence of mcr-4, the identification of mcr-4.3 in A. baumannii represented a gradual evolution of A. baumannii against colistin with a distinct type of mcr gene in the form of a novel plasmid carrying mcr-4.3 [40].
The analysis of evolutionary probabilities in mcr variants used a previously described method [41] using modified evolutionary probabilities (EPs) [42]. A user-specified tree topology was analyzed using the maximum likelihood method and the general time reversible model [43]. The evolutionary time depths used in the EP calculation can be obtained using the real-time [44] method. This analysis involved using the 10 nucleotide sequences of mcr. Codon positions included the first + second + third plus the noncoding positions. All positions containing gaps and missing data were eliminated (complete deletion option). The results, which represent the number of base differences per site for each mcr variant, are depicted in (Figure 1).
Figure 1. The probability of substitution of one base for another base. Substitution patterns and rates were estimated using the general time reversible model [45]. The maximum log-likelihood for this computation was 2655.269. This analysis involved all 10 nucleotide sequences of mcr. Codon positions included were 1st + 2nd + 3rd + noncoding. All positions containing gaps and missing data were eliminated (complete deletion option).
The probability of substitution of nucleotides to mcr-1 is demonstrated in Figure 1, which shows that the most likely substitution of adenine was with guanine (12%), of thymine was with cytosine (15%), of cytosine was with thymine (15%), and of guanine was with adenine (11%). The positions of substitution of nucleotides (A, T, G, and C from position 1 to 262 of different sites) for mcr-1 (E. coli strain ZZ1409 KU886144) are shown in Figure 2, respectively. In terms of positioning, cytosine (C) is predominately present at positions 1 to 257, followed by adenine (A) from positions 1 to 253, guanine (G) from positions 1 to 261, and thymine (T) from positions 5 to 261. In terms of probability and position of substitution, guanine was mostly likely to be present at position 27 with a probability of 0.95, and least likely to be present at position 28 with a probability of substitution of 0.007; thymine was most likely to be present at position 30 with a probability of 0.95 and least likely to be present at position 28 with a probability of 0.007; adenine was most likely to be present at position 220 with a probability of 0.94 and least likely to be present at position 27 with a probability of 0.007; cytosine was most likely to be present at position 160 with a probability of 0.93 and least likely to be present at position 262 with a probability of 0.014.
Figure 2. Depiction of the evolutionary probabilities of nucleotide substitution with respect to positions 1 to 262 for mcr-1 in Escherichia coli strain ZZ1409 KU886144.

The Processes and Molecular Vehicles Responsible for the Transmission of mcr Variants

Studies have comprehensively analyzed the genetic environments of mcr-carrying genomes using bioinformatics tools such as Geneious R8 [46] and ISfinder software [47] to demonstrate the insertion of mcr variants. The structures of recently reported insertion sequences and the names of their associated transposons are given in Table 2.
Full genome sequencing and analysis for identification of replication origin (oriC) in mcr-1-harboring plasmids from colistin-resistant isolates have identified a novel hybrid IncI2/IncFIB plasmid pGD17-2 [48]. Moreover, the co-occurrence of pGD17-2 with plasmids pGD65-3, IncI2, and pGD65-5, IncX4 has been reported in a single drug-resistant isolate (GD65), and this co-occurrence might promote the dissemination of mcr-1 under environmental selection pressure [48]. mcr-1 and other clinically significant resistant genes such as extended-spectrum β-lactamase (ESBL) blaCTX-8 and blaCTX-M-1 are related to globally identified sequence types ST10, ST46, and ST1638 in pathogenic strains of E. coli responsible for infections in humans and animals [49][50][51]. E. coli ST10 stains carrying mcr-1 have been isolated from water at a public beach in the USA where the same ST10 strain had been isolated from an infected migratory Magellanic penguin with pododermatitis [49], suggesting that the ST10 strains carrying mcr-1 can disseminate in the marine environment. E. coli mcr-1-positive environmental isolates have been isolated from German swine farms [52] and in diseased food animals in China [53], Italy, and France [54]. A plastidome analysis of mcr-1 of Enterobacterales human isolates suggested that the spread of mcr-1 among commensals such as K. pneumoniae, E. coli, and other clinical isolates could be facilitated by various promiscuous diverse plasmids [55].
Insertion sequences (ISs) or integrons can also facilitate the spread of mcr. An analysis of mcr-1 from various sources using whole genome sequencing supported a single mcr-1 mobilization event in ISApl1-mcr-1-orf-ISApl1 transposon [56]. This transposon has been immobilized on different plasmids such as IncI2, IncHI2, and IncX4 [57]. Plasmids pGD65-3, IncI2, and pGD65-5, IncX4 contain two insertion sequences, ISEcp1 and ISApl1, that facilitate the mobilization of mcr-1 [48]. The insertion sequence ISApl1, which originated in Actinobacillus pleuropneumoniae, is located upstream of mcr-1 in the IncI2-type mcr-1-harboring plasmid Phnshp45 [58][59][60]. However, the ISApl1 element is not always found associated with mcr-1 on most IncX4 plasmids [59][60][61]. A reason for this may be that the translocation of an mcr-1-pap2 element by integration of an ISApl1 cassette (a member of the IS30 family) [38][59] into plasmids such as pMCR1-IncI2, and pMCR1-IncX4 may induce the formation of circular intermediates by recognizing inverted repeat sequences, which ultimately results in loss of ISApl1 after integration of mcr-1 [38][62][63].
The mcr-2 gene is not associated with ISApl1, but there are two IS1595-like insertion sequences predicted to surround mcr-2 in the IncX4 plasmid pKP37-BE [64]. The short IS1595-like element carries a transposase gene flanked by two inverted repeats surrounding mcr-2. This transposase-encoding gene is similar (75% identity) to a fragment found in Moraxella bovoculi strain 58069, which suggests the origin of mcr-2 was from M. bovoculi [62]. The occurrence of duplicate target sites adjacent to a spacer sequence suggests that the spacer sequence is the most probable hot site in IncX4 plasmids for integration and transposition of mcr-2 variants [65]. Transfer of mcr-2 can occur through IS1595-containing transposons [62][63][65][66].
Table 2. Recently reported insertion sequences and transposon elements associated with mcr genes transmission.
mcr Variants Insertion Sequences Structure Transposon Plasmids Organism Host
(Isolated from)		 Year of Discovery References
mcr-1 (ISApl1-mcr-1-pap2-ISApl1 and Tn7511) Novel transposon Tn7511 IncI1 plasmid, pMCR-E2899 E. coli DH5α Turkey meat 2022 [67]
mcr-1 Combination of ISApl1 and IS91 (ISApl1-mcr-1-IS91) Chromosomal Tn6330 transposon IncI2 plasmid E. coli Community and hospital settings 2022 [58]
mcr-1 IS26-mcr-1-PAP2, and
ISAPl1-mcr-1-PAP2 and ISEcp1-blaCTX₋M₋₅₅-mcr-1-PAP2		 --- IncI2, IncX4, and IncHI2 plasmids E. coli and Salmonella spp. Food products, food supply chain, and clinical samples 2021 [68][69]
mcr-1.1 IS26-parA-mcr-1.1-pap2 --- IncX4-type plasmid E. coli Dog feces 2020 [56]
mcr-1 I ISApl1-mcr-1-orf ISApl1 ISApl1 transposon IncHI2 and IncX4 plasmids Enterobacteriaceae Livestock 2018 [70]
mcr-1 ISApl1-mcr-1-pap2-ISApl1 Tn6330 IncI2 and IncX4 plasmids Novel Moraxella spp. Pig 2018 [46]
mcr-1 mcr-1-orf, ISApl1-mcr-1-orf and Tn6330 Novel transposon Tn6330 IncX4 and IncI2 plasmids E. coli Pig farms in China 2017 [69]
mcr-2 (ISEc69-mcr-2-ORF-ISEc69 Tn7052 IncX4 conjugative plasmid Moraxella osloensis --- 2021 [71]
mcr-2 ISEc69-mcr-2-ISEc69 --- IncX4 plasmid M. bovoculi Pigs, pork and chicken meat, and humans 2017 [72]
mcr- 3.1 TnAs2-mcr-3.1-dgkA-ISKpn40 Novel transposon Tn6330 pCP61-IncFIB plasmid E. coli Pigs 2021 [73]
mcr-3.5 IS4321R-TnAs2-mcr-3.5-dgkA-IS15 Novel transposon Tn6330 IncFIItype plasmid pCP55-IncFII E. coli Pigs 2021 [73]
mcr-3.7 TnAs2-mcr-3.7-dgkA-IS26 --- IncP1 plasmid E. coli Dogs 2020 [56]
mcr-8 IS903B-ampC-hp-hphp-Giy-T-dgkA-baeS-copR-IS3-mcr-8-Gly-T-IS5 _ Δ IS66 transposases IncFIA plasmid K. pneumoniae Patients from intensive care 2022 [74]
mcr-8 IS903B-ymoA-inhA-mcr-8-copR-baeS-dgkA-ampC Composite transposon pABC264-OXA-181 plasmid K. pneumoniae Patient with bacteremia 2022 [75]
mcr-8.2 ISEcl1-mcr-8.2-orf-ISKpn26 --- IncFII/FIA K. pneumoniae Patient’s Intestinal sample 2022 [76]
mcr-9.1 IS903B-mcr-9.1-wbuC-IS26 Tn6360 IncHI2/2A plasmid E. cloacae complex Clinical isolates 2022 [77]
mcr-10 ISKpn26 is present at upstream of xerC-mcr-10 and an IS26 Transposon Tn1722 IncFIA plasmid Enterobacter roggenkampii Clinical isolate 2020 [78]
mcr-10.1 hsdSMR-ISEc36-mcr-10.1-xerC --- IncFIIK plasmids K. pneumoniae Clinical isolates 2022 [77]

3. Methods for Detecting Polymyxin Resistance

As resistance to polymyxins is being reported frequently among different bacterial isolates from humans, animals, and the environment, affordable, accessible, and efficient diagnostic approaches are needed. The phenotypic determination of colistin-resistant isolates can be made by growing on media such as CHROMagar COL- APSE [79], SuperPolymyxin™ [80], and LBJMR [81], as well as using commercial automated MIC-determining instruments such as BD Phoenix, MicroScan, Vitek 2 [82], MICRONAUT- S [83], and Sensititre [84]. The rapid polymyxin NP test and its modifications [85], colispot [86] colistin MAC test [87], MIC Test Strip, MICRONAUT-MIC Strip [88], the UMIC System [89], and Sensitest Colistin [84] can also be used [82]. Eazyplex SuperBug kit [90] and Taqman/SYBR Green real-time PCR assays have been used for molecular identification of mcr genes that have yielded 100% specificity and sensitivity with a rapid turnaround time (<3 h) [91]. More advanced molecular techniques such as multi-loop-mediated isothermal amplification (multi-LAMP) assays can also be used for rapid detection of mcr genes [92]. Based on cost, sensitivity and specificity, turnaround time, and the skills required to perform the test, the use of culture media or the Rapid Polymyxin Nordmann–Poirel (RPNP) test are recommended for low-resourced laboratories, while Multiplex PCR or Taqman/SYBR Green real-time PCR assays along with RPNP or novel culture media are applicable for well-resourced laboratories [93][94].
To study the evolution in mcr-positive bacterial strains, different sequencing techniques can be used including Sanger sequencing and the identification of single nucleotide polymorphisms [95] for mutational analysis or identification of new mcr- variant(s) [96]. For detailed studies of intrinsic determinants of resistance, whole genome sequencing (WGS) [97], nanopore sequencing, and transposon-directed insertion site sequencing [72] can give insights into the interactions of genetic elements associated with polymyxins resistance. To study coevolution among pairs of mcr or multiple mcr elements within a single bacterial cell, mcr-coevolution assays could be used [72].

This entry is adapted from the peer-reviewed paper 10.3390/antibiotics12111597

References

  1. Shen, Z.; Wang, Y.; Shen, Y.; Shen, J.; Wu, C. Early emergence of mcr-1 in Escherichia coli from food-producing animals. Lancet Infect. Dis. 2016, 16, 293.
  2. Wang, R.; Liu, Y.; Zhang, Q.; Jin, L.; Wang, Q.; Zhang, Y.; Wang, X.; Hu, M.; Li, L.; Qi, J.; et al. The prevalence of colistin resistance in Escherichia coli and Klebsiella pneumoniae isolated from food animals in China: Coexistence of mcr-1 and bla(NDM) with low fitness cost. Int. J. Antimicrob. Agents 2018, 51, 739–744.
  3. Kuo, S.C.; Huang, W.C.; Wang, H.Y.; Shiau, Y.R.; Cheng, M.F.; Lauderdale, T.L. Colistin resistance gene mcr-1 in Escherichia coli isolates from humans and retail meats, Taiwan. J. Antimicrob. Chemother. 2016, 71, 2327–2329.
  4. Buess, S.; Nüesch-Inderbinen, M.; Stephan, R.; Zurfluh, K. Assessment of animals as a reservoir for colistin resistance: No MCR-1/MCR-2-producing Enterobacteriaceae detected in Swiss livestock. J. Glob. Antimicrob. Resist. 2017, 8, 33–34.
  5. Girardello, R.; Piroupo, C.M.; Martins, J., Jr.; Maffucci, M.H.; Cury, A.P.; Franco, M.R.G.; Malta, F.M.; Rocha, N.C.; Pinho, J.R.R.; Rossi, F.; et al. Genomic characterization of mcr-1.1-producing Escherichia coli recovered from human infections in São Paulo, Brazil. Front. Microbiol. 2021, 12, 663414.
  6. Figueiredo, R.; Card, R.M.; Nunez, J.; Pomba, C.; Mendonça, N.; Anjum, M.F.; Da Silva, G.J. Detection of an mcr-1-encoding plasmid mediating colistin resistance in Salmonella enterica from retail meat in Portugal. J. Antimicrob. Chemother. 2016, 71, 2338–2340.
  7. Gogry, F.A.; Siddiqui, M.T.; Haq, Q.M.R. Emergence of mcr-1 conferred colistin resistance among bacterial isolates from urban sewage water in India. Environ. Sci. Pollut. Res. Int. 2019, 26, 33715–33717.
  8. Bilal, H.; Rehman, T.U.; Khan, M.A.; Hameed, F.; Jian, Z.G.; Han, J.; Yang, X. Molecular epidemiology of mcr-1, bla (KPC-2,) and bla (NDM-1) harboring clinically isolated Escherichia coli from Pakistan. Infect. Drug Resist. 2021, 14, 1467–1479.
  9. Vu Thi Ngoc, B.; Le Viet, T.; Nguyen Thi Tuyet, M.; Nguyen Thi Hong, T.; Nguyen Thi Ngoc, D.; Le Van, D.; Chu Thi, L.; Tran Huy, H.; Penders, J.; Wertheim, H.; et al. Characterization of genetic elements carrying mcr-1 gene in Escherichia coli from the community and hospital settings in Vietnam. Microbiol. Spectr. 2022, 10, e0135621.
  10. Hadjadj, L.; Baron, S.A.; Olaitan, A.O.; Morand, S.; Rolain, J.M. Co-occurrence of variants of mcr-3 and mcr-8 Genes in a Klebsiella pneumoniae isolate from Laos. Front. Microbiol. 2019, 10, 2720.
  11. McGann, P.; Snesrud, E.; Maybank, R.; Corey, B.; Ong, A.C.; Clifford, R.; Hinkle, M.; Whitman, T.; Lesho, E.; Schaecher, K.E. Escherichia coli harboring mcr-1 and blaCTX-M on a novel IncF plasmid: First report of mcr-1 in the United States. Antimicrob. Agents Chemother. 2016, 60, 4420–4421.
  12. Cannatelli, A.; Giani, T.; Antonelli, A.; Principe, L.; Luzzaro, F.; Rossolini, G.M. First detection of the mcr-1 colistin resistance gene in Escherichia coli in Italy. Antimicrob. Agents Chemother. 2016, 60, 3257–3258.
  13. Kawanishi, M.; Abo, H.; Ozawa, M.; Uchiyama, M.; Shirakawa, T.; Suzuki, S.; Shima, A.; Yamashita, A.; Sekizuka, T.; Kato, K.; et al. Prevalence of colistin resistance gene mcr-1 and absence of mcr-2 in Escherichia coli isolated from healthy food-producing animals in Japan. Antimicrob. Agents Chemother. 2017, 61, e02057-16.
  14. Bhat, A.H. Bacterial zoonoses transmitted by household pets and as reservoirs of antimicrobial resistant bacteria. Microb. Pathog. 2021, 155, 104891.
  15. Skarżyńska, M.; Zaja, C.M.; Bomba, A.; Bocian, Ł.; Kozdruń, W.; Polak, M.; Wia Cek, J.; Wasyl, D. Antimicrobial resistance glides in the Sky-Free-Living Birds as a reservoir of resistant Escherichia coli with zoonotic potential. Front. Microbiol. 2021, 12, 656223.
  16. Zurfluh, K.; Nüesch-Inderbinen, M.; Klumpp, J.; Poirel, L.; Nordmann, P.; Stephan, R. Key features of mcr-1-bearing plasmids from Escherichia coli isolated from humans and food. Antimicrob. Resist. Infect. Control 2017, 6, 91.
  17. Fernandes, M.R.; Sellera, F.P.; Esposito, F.; Sabino, C.P.; Cerdeira, L.; Lincopan, N. Colistin-resistant mcr-1-positive Escherichia coli on public beaches, an infectious threat emerging in recreational waters. Antimicrob. Agents Chemother. 2017, 61, e00234-17.
  18. Zhao, F.; Feng, Y.; Lü, X.; McNally, A.; Zong, Z. IncP plasmid carrying colistin resistance gene mcr-1 in Klebsiella pneumoniae from hospital sewage. Antimicrob. Agents Chemother. 2017, 61, e02229-16.
  19. Hembach, N.; Schmid, F.; Alexander, J.; Hiller, C.; Rogall, E.T.; Schwartz, T. Occurrence of the mcr-1 colistin resistance gene and other clinically relevant antibiotic resistance genes in microbial populations at different municipal wastewater treatment plants in Germany. Front. Microbiol. 2017, 8, 1282.
  20. Sun, P.; Bi, Z.; Nilsson, M.; Zheng, B.; Berglund, B.; Stålsby Lundborg, C.; Börjesson, S.; Li, X.; Chen, B.; Yin, H.; et al. Occurrence of bla(KPC-2), bla(CTX-M), and mcr-1 in Enterobacteriaceae from Well Water in Rural China. Antimicrob. Agents Chemother. 2017, 61, e02569-16.
  21. Zhang, J.; Wang, J.; Chen, L.; Yassin, A.K.; Kelly, P.; Butaye, P.; Li, J.; Gong, J.; Cattley, R.; Qi, K.; et al. Housefly (Musca domestica) and blow fly (Protophormia terraenovae) as vectors of bacteria carrying colistin resistance genes. Appl. Environ. Microbiol. 2018, 84, e01736-17.
  22. Bean, D.C.; Wigmore, S.M.; Abdul Momin, M.H.F.; Wareham, D.W. Polymyxin resistant bacteria in Australian poultry. Front. Sustain. Food Syst. 2020, 4, 550318.
  23. Yoon, E.J.; Hong, J.S.; Yang, J.W.; Lee, K.J.; Lee, H.; Jeong, S.H. Detection of mcr-1 plasmids in Enterobacteriaceae isolates from human specimens: Comparison with those in Escherichia coli isolates from livestock in Korea. Ann. Lab. Med. 2018, 38, 555–562.
  24. Zeng, K.J.; Doi, Y.; Patil, S.; Huang, X.; Tian, G.B. Emergence of the plasmid-mediated mcr-1 gene in colistin-resistant Enterobacter aerogenes and Enterobacter cloacae. Antimicrob. Agents Chemother. 2016, 60, 3862–3863.
  25. Liu, B.T.; Song, F.J.; Zou, M.; Hao, Z.H.; Shan, H. Emergence of colistin resistance gene mcr-1 in Cronobacter sakazakii producing NDM-9 and in Escherichia coli from the same animal. Antimicrob. Agents Chemother. 2017, 61, 01444-16.
  26. Li, X.P.; Fang, L.X.; Jiang, P.; Pan, D.; Xia, J.; Liao, X.P.; Liu, Y.H.; Sun, J. Emergence of the colistin resistance gene mcr-1 in Citrobacter freundii. Int. J. Antimicrob. Agents 2017, 49, 786–787.
  27. Mendes, A.C.; Novais, Â.; Campos, J.; Rodrigues, C.; Santos, C.; Antunes, P.; Ramos, H.; Peixe, L. mcr-1 in carbapenemase-producing Klebsiella pneumoniae with hospitalized patients, Portugal, 2016–2017. Emerg. Infect. Dis. 2018, 24, 762–766.
  28. Yi, L.; Wang, J.; Gao, Y.; Liu, Y.; Doi, Y.; Wu, R.; Zeng, Z.; Liang, Z.; Liu, J.H. mcr-1-harboring Salmonella enterica serovar Typhimurium sequence type 34 in pigs, China. Emerg. Infect. Dis. 2017, 23, 291–295.
  29. Ma, Q.; Huang, Y.; Wang, J.; Xu, X.; Hawkey, J.; Yang, C.; Liang, B.; Hu, X.; Wu, F.; Yang, X.; et al. Multidrug-resistant Shigella sonnei carrying the plasmid-mediated mcr-1 gene in China. Int. J. Antimicrob. Agents 2018, 52, 14–21.
  30. Luo, J.; Yao, X.; Lv, L.; Doi, Y.; Huang, X.; Huang, S.; Liu, J.H. Emergence of mcr-1 in Raoultella ornithinolytica and Escherichia coli isolates from retail vegetables in China. Antimicrob. Agents Chemother. 2017, 61, e01139-17.
  31. He, Z.; Yang, Y.; Li, W.; Ma, X.; Zhang, C.; Zhang, J.; Sun, B.; Ding, T.; Tian, G.B. Comparative genomic analyses of polymyxin-resistant Enterobacteriaceae strains from China. BMC Genom. 2022, 23, 88.
  32. Ellem, J.A.; Ginn, A.N.; Chen, S.C.; Ferguson, J.; Partridge, S.R.; Iredell, J.R. Locally acquired mcr-1 in Escherichia coli, Australia, 2011 and 2013. Emerg. Infect. Dis. 2017, 23, 1160–1163.
  33. Bell, J.M.; Lubian, A.F.; Partridge, S.R.; Gottlieb, T.; Iredell, J.; Daley, D.A.; Coombs, G.W. Australian Group on Antimicrobial Resistance (AGAR) Australian Gram-negative Sepsis Outcome Programme (GnSOP) Annual Report 2020. Commun. Dis. Intell. 2022, 46, 1–12.
  34. Arnott, A.; Wang, Q.; Bachmann, N.; Sadsad, R.; Biswas, C.; Sotomayor, C.; Howard, P.; Rockett, R.; Wiklendt, A.; Iredell, J.R.; et al. Multidrug-resistant Salmonella enterica 4,,12:i:- Sequence Type 34, New South Wales, Australia, 2016–2017. Emerg. Infect. Dis. 2018, 24, 751.
  35. Ingle, D.J.; Ambrose, R.L.; Baines, S.L.; Duchene, S.; Gonçalves da Silva, A.; Lee, D.Y.J.; Jones, M.; Valcanis, M.; Taiaroa, G.; Ballard, S.A.; et al. Evolutionary dynamics of multidrug resistant Salmonella enterica serovar 4,,12:i:- in Australia. Nat. Commun. 2021, 12, 4786.
  36. Xiang, R.; Liu, B.H.; Zhang, A.Y.; Lei, C.W.; Ye, X.L.; Yang, Y.X.; Chen, Y.P.; Wang, H.N. Colocation of the polymyxin resistance gene mcr-1 and a variant of mcr-3 on a plasmid in an Escherichia coli isolate from a chicken farm. Antimicrob. Agents Chemother. 2018, 62, e00501-18.
  37. Belaynehe, K.M.; Shin, S.W.; Park, K.Y.; Jang, J.Y.; Won, H.G.; Yoon, I.J.; Yoo, H.S. Emergence of mcr-1 and mcr-3 variants coding for plasmid-mediated colistin resistance in Escherichia coli isolates from food-producing animals in South Korea. Int. J. Infect. Dis. 2018, 72, 22–24.
  38. Sun, J.; Fang, L.X.; Wu, Z.; Deng, H.; Yang, R.S.; Li, X.P.; Li, S.M.; Liao, X.P.; Feng, Y.; Liu, Y.H. Genetic analysis of the IncX4 plasmids: Implications for a unique pattern in the mcr-1 acquisition. Sci. Rep. 2017, 7, 424.
  39. Zhang, J.; Chen, L.; Wang, J.; Yassin, A.K.; Butaye, P.; Kelly, P.; Gong, J.; Guo, W.; Li, J.; Li, M.; et al. Molecular detection of colistin resistance genes (mcr-1, mcr-2 and mcr-3) in nasal/oropharyngeal and anal/cloacal swabs from pigs and poultry. Sci. Rep. 2018, 8, 3705.
  40. Martins-Sorenson, N.; Snesrud, E.; Xavier, D.E.; Cacci, L.C.; Iavarone, A.T.; McGann, P.; Riley, L.W.; Moreira, B.M. A novel plasmid-encoded mcr-4.3 gene in a colistin-resistant Acinetobacter baumannii clinical strain. J. Antimicrob. Chemother. 2020, 75, 60–64.
  41. Patel, R.; Kumar, S. On estimating evolutionary probabilities of population variants. BMC Evol. Biol. 2019, 19, 133.
  42. Nei, M.; Kumar, S. Molecular Evolution and Phylogenetics; Oxford University Press: New York, NY, USA, 2000.
  43. Tamura, K.; Tao, Q.; Kumar, S. Theoretical Foundation of the RelTime method for estimating divergence times from variable evolutionary rates. Mol. Biol. Evol. 2018, 35, 1770–1782.
  44. Humphrey, S.; Fillol-Salom, A.; Quiles-Puchalt, N.; Ibarra-Chávez, R.; Haag, A.F.; Chen, J.; Penadés, J.R. Bacterial chromosomal mobility via lateral transduction exceeds that of classical mobile genetic elements. Nat. Commun. 2021, 12, 6509.
  45. El-Sayed Ahmed, M.A.E.; Zhong, L.L.; Shen, C.; Yang, Y.; Doi, Y.; Tian, G.B. Colistin and its role in the Era of antibiotic resistance: An extended review (2000–2019). Emerg. Microbes Infect. 2020, 9, 868–885.
  46. Strepis, N.; Voor In ‘t Holt, A.F.; Vos, M.C.; Zandijk, W.H.A.; Heikema, A.P.; Hays, J.P.; Severin, J.A.; Klaassen, C.H.W. Genetic analysis of mcr-1-carrying plasmids from Gram-negative bacteria in a Dutch tertiary care hospital: Evidence for intrapatient and interspecies transmission events. Front. Microbiol. 2021, 12, 727435.
  47. Goodman, R.N.; Tansirichaiya, S.; Brouwer, M.S.M.; Roberts, A.P. Intracellular transposition of mobile genetic elements associated with the colistin resistance gene mcr-1. Microbiol. Spectr. 2023, 11, e0327822.
  48. Wang, Q.; Sun, J.; Li, J.; Ding, Y.; Li, X.P.; Lin, J.; Hassan, B.; Feng, Y. Expanding landscapes of the diversified mcr-1-bearing plasmid reservoirs. Microbiome 2017, 5, 70.
  49. Sellera, F.P.; Fernandes, M.R.; Sartori, L.; Carvalho, M.P.; Esposito, F.; Nascimento, C.L.; Dutra, G.H.; Mamizuka, E.M.; Pérez-Chaparro, P.J.; McCulloch, J.A.; et al. Escherichia coli carrying IncX4 plasmid-mediated mcr-1 and blaCTX-M genes in infected migratory Magellanic penguins (Spheniscus magellanicus). J. Antimicrob. Chemother. 2017, 72, 1255–1256.
  50. Maluta, R.P.; Logue, C.M.; Casas, M.R.; Meng, T.; Guastalli, E.A.; Rojas, T.C.; Montelli, A.C.; Sadatsune, T.; de Carvalho Ramos, M.; Nolan, L.K.; et al. Overlapped sequence types (STs) and serogroups of avian pathogenic (APEC) and human extra-intestinal pathogenic (ExPEC) Escherichia coli isolated in Brazil. PLoS ONE 2014, 9, e105016.
  51. Mshana, S.E.; Imirzalioglu, C.; Hain, T.; Domann, E.; Lyamuya, E.F.; Chakraborty, T. Multiple ST clonal complexes, with a predominance of ST131, of Escherichia coli harbouring blaCTX-M-15 in a tertiary hospital in Tanzania. Clin. Microbiol. Infect. 2011, 17, 1279–1282.
  52. Guenther, S.; Falgenhauer, L.; Semmler, T.; Imirzalioglu, C.; Chakraborty, T.; Roesler, U.; Roschanski, N. Environmental emission of multiresistant Escherichia coli carrying the colistin resistance gene mcr-1 from German swine farms. J. Antimicrob. Chemother. 2017, 72, 1289–1292.
  53. Wang, Y.; Zhang, R.; Li, J.; Wu, Z.; Yin, W.; Schwarz, S.; Tyrrell, J.M.; Zheng, Y.; Wang, S.; Shen, Z.; et al. Comprehensive resistome analysis reveals the prevalence of NDM and MCR-1 in Chinese poultry production. Nat. Microbiol. 2017, 2, 16260.
  54. El Garch, F.; Sauget, M.; Hocquet, D.; LeChaudee, D.; Woehrle, F.; Bertrand, X. mcr-1 is borne by highly diverse Escherichia coli isolates since 2004 in food-producing animals in Europe. Clin. Microbiol. Infect. 2017, 23, 51.e51–51.e54.
  55. Boueroy, P.; Wongsurawat, T.; Jenjaroenpun, P.; Chopjitt, P.; Hatrongjit, R.; Jittapalapong, S.; Kerdsin, A. Plasmidome in mcr-1 harboring carbapenem-resistant Enterobacterales isolates from human in Thailand. Sci. Rep. 2022, 12, 19051.
  56. Wang, R.; van Dorp, L.; Shaw, L.P.; Bradley, P.; Wang, Q.; Wang, X.; Jin, L.; Zhang, Q.; Liu, Y.; Rieux, A.; et al. The global distribution and spread of the mobilized colistin resistance gene mcr-1. Nat. Commun. 2018, 9, 1179.
  57. Matamoros, S.; van Hattem, J.M.; Arcilla, M.S.; Willemse, N.; Melles, D.C.; Penders, J.; Vinh, T.N.; Thi Hoa, N.; Bootsma, M.C.J.; van Genderen, P.J.; et al. Global phylogenetic analysis of Escherichia coli and plasmids carrying the mcr-1 gene indicates bacterial diversity but plasmid restriction. Sci. Rep. 2017, 7, 15364.
  58. Liu, Y.Y.; Wang, Y.; Walsh, T.R.; Yi, L.X.; Zhang, R.; Spencer, J.; Doi, Y.; Tian, G.; Dong, B.; Huang, X.; et al. Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: A microbiological and molecular biological study. Lancet Infect. Dis. 2016, 16, 161–168.
  59. Wang, Q.; Sun, J.; Ding, Y.; Li, X.P.; Liu, Y.H.; Feng, Y. Genomic insights into mcr-1-positive plasmids carried by colistin-resistant Escherichia coli isolates from inpatients. Antimicrob. Agents Chemother. 2017, 61, e00361-17.
  60. Tegetmeyer, H.E.; Jones, S.C.; Langford, P.R.; Baltes, N. ISApl1, a novel insertion element of Actinobacillus pleuropneumoniae, prevents ApxIV-based serological detection of serotype 7 strain AP76. Vet. Microbiol. 2008, 128, 342–353.
  61. Geurts, A.M.; Hackett, C.S.; Bell, J.B.; Bergemann, T.L.; Collier, L.S.; Carlson, C.M.; Largaespada, D.A.; Hackett, P.B. Structure-based prediction of insertion-site preferences of transposons into chromosomes. Nucleic Acids Res. 2006, 34, 2803–2811.
  62. Sun, J.; Xu, Y.; Gao, R.; Lin, J.; Wei, W.; Srinivas, S.; Li, D.; Yang, R.S.; Li, X.P.; Liao, X.P.; et al. Deciphering MCR-2 colistin resistance. mBio 2017, 8, e00625-17.
  63. Xavier, B.B.; Lammens, C.; Ruhal, R.; Kumar-Singh, S.; Butaye, P.; Goossens, H.; Malhotra-Kumar, S. Identification of a novel plasmid-mediated colistin-resistance gene, mcr-2, in Escherichia coli, Belgium, June 2016. EuroSurveill 2016, 21, 30280.
  64. Le, S.Q.; Gascuel, O. An improved general amino acid replacement matrix. Mol. Biol. Evol. 2008, 25, 1307–1320.
  65. Cain, A.K.; Liu, X.; Djordjevic, S.P.; Hall, R.M. Transposons related to Tn1696 in IncHI2 plasmids in multiply antibiotic resistant Salmonella enterica serovar Typhimurium from Australian animals. Microb. Drug Resist. 2010, 16, 197–202.
  66. Snesrud, E.; McGann, P.; Chandler, M. The birth and demise of the ISApl1-mcr-1-ISApl1 composite transposon: The vehicle for transferable colistin resistance. mBio 2018, 9, e02381-17.
  67. Li, W.; Yan, Y.; Chen, J.; Sun, R.; Wang, Y.; Wang, T.; Feng, Z.; Peng, K.; Wang, J.; Chen, S.J. Genomic characterization of conjugative plasmids carrying the mcr-1 gene in foodborne and clinical strains of Salmonella and Escherichia coli. Food Control. 2021, 125, 108032.
  68. Du, C.; Feng, Y.; Wang, G.; Zhang, Z.; Hu, H.; Yu, Y.; Liu, J.; Qiu, L.; Liu, H.; Guo, Z.; et al. Co-occurrence of the mcr-1.1 and mcr-3.7 genes in a multidrug-resistant Escherichia coli isolate from China. Infect. Drug Resist. 2020, 13, 3649–3655.
  69. He, Y.Z.; Long, T.F.; He, B.; Li, X.P.; Li, G.; Chen, L.; Liao, X.P.; Liu, Y.H.; Sun, J. ISEc69-mediated mobilization of the colistin resistance gene mcr-2 in Escherichia coli. Front. Microbiol. 2020, 11, 564973.
  70. Li, R.; Xie, M.; Zhang, J.; Yang, Z.; Liu, L.; Liu, X.; Zheng, Z.; Chan, E.W.; Chen, S. Genetic characterization of mcr-1-bearing plasmids to depict molecular mechanisms underlying dissemination of the colistin resistance determinant. J. Antimicrob. Chemother. 2017, 72, 393–401.
  71. Partridge, S.R. mcr-2 in the IncX4 plasmid pKP37-BE is flanked by directly oriented copies of ISEc69. J. Antimicrob. Chemother. 2017, 72, 1533–1535.
  72. Li, R.; Du, P.; Zhang, P.; Li, Y.; Yang, X.; Wang, Z.; Wang, J.; Bai, L. Comprehensive genomic investigation of coevolution of mcr genes in Escherichia coli strains via nanopore sequencing. Glob. Chall. 2021, 5, 2000014.
  73. Bai, S.C.; Li, R.B.; Yang, Y.; Liao, X.P. Sporadic dissemination of mcr-8-ST11 Klebsiella pneumoniae isolates in China. Enferm. Infecc. Microbiol. Clin. 2022, 40, 95–97.
  74. Ge, H.; Qiao, J.; Xu, H.; Liu, R.; Chen, R.; Li, C.; Hu, X.; Zhou, J.; Guo, X.; Zheng, B. First report of Klebsiella pneumoniae co-producing OXA-181, CTX-M-55, and MCR-8 isolated from the patient with bacteremia. Front. Microbiol. 2022, 13, 1020500.
  75. Liu, C.; Wu, Y.; Fang, Y.; Sang, Z.; Huang, L.; Dong, N.; Zeng, Y.; Lu, J.; Zhang, R.; Chen, G. Emergence of an ST1326 (CG258) multi-drug resistant Klebsiella pneumoniae co-harboring mcr-8.2, ESBL genes, and the resistance-nodulation-division efflux pump gene cluster tmexCD1-toprJ1 in China. Front. Microbiol. 2022, 13, 800993.
  76. Jiang, S.; Wang, X.; Yu, H.; Zhang, J.; Wang, J.; Li, J.; Li, X.; Hu, K.; Gong, X.; Gou, X.; et al. Molecular antibiotic resistance mechanisms and co-transmission of the mcr-9 and metallo-β-lactamase genes in carbapenem-resistant Enterobacter cloacae complex. Front. Microbiol. 2022, 13, 1032833.
  77. Liu, M.C.; Jian, Z.; Liu, W.; Li, J.; Pei, N. One healthaAnalysis of mcr-carrying plasmids and emergence of mcr-10.1 in three species of Klebsiella recovered from humans in China. Microbiol. Spectr. 2022, 10, e0230622.
  78. Wang, C.; Feng, Y.; Liu, L.; Wei, L.; Kang, M.; Zong, Z. Identification of novel mobile colistin resistance gene mcr-10. Emerg. Microbes Infect. 2020, 9, 508–516.
  79. Abdul Momin, M.H.F.; Bean, D.C.; Hendriksen, R.S.; Haenni, M.; Phee, L.M.; Wareham, D.W. CHROMagar COL-APSE: A selective bacterial culture medium for the isolation and differentiation of colistin-resistant Gram-negative pathogens. J. Med. Microbiol. 2017, 66, 1554–1561.
  80. Przybysz, S.M.; Correa-Martinez, C.; Köck, R.; Becker, K.; Schaumburg, F. SuperPolymyxin™ medium for the screening of colistin-resistant gram-negative bacteria in stool samples. Front. Microbiol. 2018, 9, 2809.
  81. Bardet, L.; Le Page, S.; Leangapichart, T.; Rolain, J.M. LBJMR medium: A new polyvalent culture medium for isolating and selecting vancomycin and colistin-resistant bacteria. BMC Microbiol. 2017, 17, 220.
  82. Zhou, M.; Wang, Y.; Liu, C.; Kudinha, T.; Liu, X.; Luo, Y.; Yang, Q.; Sun, H.; Hu, J.; Xu, Y.C. Comparison of five commonly used automated susceptibility testing methods for accuracy in the China Antimicrobial Resistance Surveillance System (CARSS) hospitals. Infect. Drug Resist. 2018, 11, 1347–1358.
  83. Cordovana, M.; Ambretti, S. Antibiotic susceptibility testing of anaerobic bacteria by broth microdilution method using the MICRONAUT-S Anaerobes MIC plates. Anaerobe 2020, 63, 102217.
  84. Carretto, E.; Brovarone, F.; Russello, G.; Nardini, P.; El-Bouseary, M.M.; Aboklaish, A.F.; Walsh, T.R.; Tyrrell, J.M. Clinical validation of SensiTest colistin, a broth microdilution-based nethod to evaluate colistin MICs. J. Clin. Microbiol. 2018, 56, e01523-17.
  85. Poirel, L.; Larpin, Y.; Dobias, J.; Stephan, R.; Decousser, J.W.; Madec, J.Y.; Nordmann, P. Rapid Polymyxin NP test for the detection of polymyxin resistance mediated by the mcr-1/mcr-2 genes. Diagn. Microbiol. Infect. Dis. 2018, 90, 7–10.
  86. Jouy, E.; Haenni, M.; Le Devendec, L.; Le Roux, A.; Châtre, P.; Madec, J.Y.; Kempf, I. Improvement in routine detection of colistin resistance in E. coli isolated in veterinary diagnostic laboratories. J. Microbiol. Methods 2017, 132, 125–127.
  87. Coppi, M.; Cannatelli, A.; Antonelli, A.; Baccani, I.; Di Pilato, V.; Sennati, S.; Giani, T.; Rossolini, G.M. A simple phenotypic method for screening of MCR-1-mediated colistin resistance. Clin. Microbiol. Infect. 2018, 24, 201.e201–201.e203.
  88. Kon, H.; Dalak, M.A.B.; Schwartz, D.; Carmeli, Y.; Lellouche, J. Evaluation of the MICRONAUT MIC-strip colistin assay for colistin susceptibility testing of carbapenem-resistant Acinetobacter baumannii and Enterobacterales. Diagn. Microbiol. Infect. Dis. 2021, 100, 115391.
  89. Bardet, L.; Okdah, L.; Le Page, S.; Baron, S.A.; Rolain, J.M. Comparative evaluation of the UMIC Colistine kit to assess MIC of colistin of gram-negative rods. BMC Microbiol. 2019, 19, 60.
  90. Sękowska, A.; Bogiel, T. The Evaluation of Eazyplex® SuperBug CRE assay usefulness for the detection of ESBLs and carbapenemases genes directly from urine samples and positive blood cultures. Antibiotics 2022, 11, 138.
  91. Chabou, S.; Leangapichart, T.; Okdah, L.; Le Page, S.; Hadjadj, L.; Rolain, J.M. Real-time quantitative PCR assay with Taqman® probe for rapid detection of MCR-1 plasmid-mediated colistin resistance. New Microbes New Infect. 2016, 13, 71–74.
  92. Zhong, L.L.; Zhou, Q.; Tan, C.Y.; Roberts, A.P.; El-Sayed Ahmed, M.A.E.; Chen, G.; Dai, M.; Yang, F.; Xia, Y.; Liao, K.; et al. Multiplex loop-mediated isothermal amplification (multi-LAMP) assay for rapid detection of mcr-1 to mcr-5 in colistin-resistant bacteria. Infect. Drug Resist. 2019, 12, 1877–1887.
  93. Borowiak, M.; Baumann, B.; Fischer, J.; Thomas, K.; Deneke, C.; Hammerl, J.A.; Szabo, I.; Malorny, B. Development of a novel mcr-6 to mcr-9 multiplex PCR and assessment of mcr-1 to mcr-9 occurrence in colistin-resistant Salmonella enterica isolates from environment, feed, animals and food (2011–2018) in Germany. Front. Microbiol. 2020, 11, 80.
  94. Li, J.; Shi, X.; Yin, W.; Wang, Y.; Shen, Z.; Ding, S.; Wang, S. A multiplex SYBR green real-time PCR assay for the detection of three colistin resistance genes from cultured bacteria, feces, and environment samples. Front. Microbiol. 2017, 8, 2078.
  95. Neumann, B.; Rackwitz, W.; Hunfeld, K.P.; Fuchs, S.; Werner, G.; Pfeifer, Y. Genome sequences of two clinical Escherichia coli isolates harboring the novel colistin-resistance gene variants mcr-1.26 and mcr-1.27. Gut Pathog. 2020, 12, 40.
  96. Nicolas, I.; Bordeau, V.; Bondon, A.; Baudy-Floc’h, M.; Felden, B. Novel antibiotics effective against gram-positive and -negative multi-resistant bacteria with limited resistance. PLoS Biol. 2019, 17, e3000337.
  97. Flament-Simon, S.C.; de Toro, M.; Mora, A.; García, V.; García-Meniño, I.; Díaz-Jiménez, D.; Herrera, A.; Blanco, J. Whole genome sequencing and characteristics of mcr-1-harboring plasmids of porcine Escherichia coli isolates belonging to the high-risk clone O25b:H4-ST131 clade B. Front. Microbiol. 2020, 11, 387.
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