Chromosomally Encoded
            <i>mcr-5</i>
            in Colistin-Nonsusceptible Pseudomonas aeruginosa

Snesrud, Erik; Maybank, Rosslyn; Kwak, Yoon I.; Jones, Anthony R.; Hinkle, Mary; McGann, Patrick

doi:10.1128/aac.00679-18

Cited by 48 publications

(35 citation statements)

References 17 publications

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“…S4). This structure was previously described as a putative mobile insertion cassette (22). In both plasmid types observed in this study, the 3,803-bp putative mobile insertion cassette is flanked by 5-bp direct repeats.…”

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confidence: 61%

“…S4). However, the mobility of these elements remains to be explored, as stated previously (22). Interestingly, the frameshift mutation in major facilitator superfamily (MFS)type transporter gene proP, which led to a premature stop codon and resulted in two open reading frames in the Tn6452 transposon observed in pSE13-SA01718, was not detected in the 3,803-bp putative mobile insertion cassettes.…”

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confidence: 95%

“…Generally, the high variation of mcr-5-carrying plasmids in only eight analyzed Salmonella isolates as well as the presence of Tn6452 in two of the host genomes indicate a high mcr-5 mobility, an independent acquisition of mcr-5-harboring plasmids by individual strains, and a successful integration in and adaptation to different genomic environments. This is supported by the increasing number of publications reporting the presence of mcr-5 in various bacterial species worldwide (10,(15)(16)(17)(18)(19)(20)(21)(22)(23). However, mcr-5 is only reported sporadically, and so far, no links can be made between isolates from the environment, livestock, food, and humans.…”

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confidence: 96%

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Characterization of mcr-5 -Harboring Salmonella enterica subsp. enterica Serovar Typhimurium Isolates from Animal and Food Origin in Germany

Blettner

Hammerl

Deneke

et al. 2019

Antimicrob Agents Chemother

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We characterized eight mcr-5-positive Salmonella enterica subsp. enterica serovar Typhimurium sequence type 34 (ST34) isolates obtained from pigs and meat in Germany. Five plasmid types were identified harboring mcr-5 on Tn6452 or putative mobile insertion cassettes. The mobility of mcr-5 was confirmed by integration of Tn6452 into the bacterial chromosomes of two strains and the detection of conjugative mcr-5 plasmids. The association with mobile genetic elements might further enhance mcr-5 distribution.

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confidence: 61%

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confidence: 95%

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confidence: 96%

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Characterization of mcr-5 -Harboring Salmonella enterica subsp. enterica Serovar Typhimurium Isolates from Animal and Food Origin in Germany

Blettner

Hammerl

Deneke

et al. 2019

Antimicrob Agents Chemother

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“…The 7.7 kb variable region (VR1, Figure 2) previously detected in pBT2101 was absent from any of the other members of the megaplasmids group. Further homology searches focusing on VR1 only identified one match in GenBank, corresponding to the chromosome of the strain MRSN12280, which was recently described as the first report of a P. aeruginosa colistin-nonsusceptible isolate carrying the resistance gene mcr (63) . However, annotation of the 7.7 kb pBT2101 unique region identified only some putative genes encoding transposable phage-related proteins, suggesting that this region does not contribute to the resistance.…”

Section: The Family Of Pbt2436-like Megaplasmids Is Widely Distributementioning

confidence: 99%

A megaplasmid family responsible for dissemination of multidrug resistance inPseudomonas

Cazares

Moore

Grimes

et al. 2019

Preprint

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Multidrug resistance (MDR) represents a global threat to health. Although plasmids can play an important role in the dissemination of MDR, they have not been commonly linked to the emergence of antimicrobial resistance in the pathogen Pseudomonas aeruginosa . We used whole genome sequencing to characterize a collection of P. aeruginosa clinical isolates from a hospital in Thailand. Using long-read sequence data we obtained complete sequences of two closely related megaplasmids (>420 kb) carrying large arrays of antibiotic resistance genes located in discrete, complex and dynamic resistance regions, and revealing evidence of extensive duplication and recombination events. A comprehensive pangenomic and phylogenomic analysis indicated that 1) these large plasmids comprise a family present in different members of the Pseudomonas genus and associated with multiple sources (geographical, clinical or environmental); 2) the megaplasmids encode diverse niche-adaptive accessory traits, including multidrug resistance; 3) the pangenome of the megaplasmid family is highly flexible and diverse, comprising a substantial core genome (average of 48% of plasmid genes), but with individual members carrying large numbers of unique genes. The history of the megaplasmid family, inferred from our analysis of the available database, suggests that members carrying multiple resistance genes date back to at least the 1970s.

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“…Table S1). Interestingly, as Pseudomonas genus where MCR-5 has been already reported 24 , all bacteria from this subtree (fig. 2D) have been originating from water, soil and environment (Suppl.…”

Section: Resultsmentioning

confidence: 68%

Massive analysis of 64’628 bacterial genomes to decipher a water reservoir and origin of mobile colistin resistance (mcr) gene variants: is there another role for this family of enzymes?

Khedher

Baron

Riziki

et al. 2019

Preprint

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20Since 2015, new worrying colistin resistance mechanism, mediated by mcr-1 21 gene has been reported worldwide along with eight newly described variants (mcr-2 to mcr-9) 22 but their source(s) and reservoir(s) remain largely unexplored. Here, we conducted a massive 23 bioinformatic analysis of 64'628 downloaded bacterial genomes to investigate the reservoir 24 and origin of these mcr variants. We identified a total of 6'651 significant positive hits (aa 25 sequence coverage > 90 % and similarity >50%) with the nine MCR variants from these 26 genomes that include 39 bacterial genera and more than 1050 species. Although these variants 27 could be identified in bacteria from human and animal sources, we found plenty MCR 28 variants in unsuspected bacteria from environmental origin, especially from water sources. 29The ubiquitous presence of mcr variants in bacteria from water likely suggests another role in 30 the biosphere of these enzymes as an unknown defense system against natural antimicrobial 31 peptides and/or bacteriophage predation. 32 21.Ling, Z. et al. Chromosome-mediated mcr-3 variants in aeromonas veronii from chicken meat. 440Antimicrob. Agents Chemother. 61, (2017). 441 22. Huang, M. et al. Action and mechanism of the colistin resistance enzyme MCR-4. Commun. 442 Biol. 2, (2019).443 23. Carroll, L. M. et al. Identification of Novel Mobilized Colistin Resistance Gene mcr-9 in a 595Suppl. Figure S2. Phylogenetic tree performed from MCR variant hits (n=6'648 proteins) with aa identity between 50% and 100% and 596 alignment ≥ 90%. 597

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Chromosomally Encoded mcr-5 in Colistin-Nonsusceptible Pseudomonas aeruginosa

Cited by 48 publications

References 17 publications

Characterization of mcr-5 -Harboring Salmonella enterica subsp. enterica Serovar Typhimurium Isolates from Animal and Food Origin in Germany

Characterization of mcr-5 -Harboring Salmonella enterica subsp. enterica Serovar Typhimurium Isolates from Animal and Food Origin in Germany

A megaplasmid family responsible for dissemination of multidrug resistance inPseudomonas

Massive analysis of 64’628 bacterial genomes to decipher a water reservoir and origin of mobile colistin resistance (mcr) gene variants: is there another role for this family of enzymes?

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