Sequence Duplication Within <i>pmrB</i> Gene Contribute to High-Level Colistin Resistance in Avian Pathogenic <i>Escherichia coli</i>

Huang, Jinhu; Dai, Xingyang; Ge, Lin; Shafiq, Muhammad; Shah, Jan Mohammad; Sun, Jianzhong; Yi, Sida; Wang, Liping

doi:10.1089/mdr.2019.0290

Cited by 2 publications

(1 citation statement)

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“…The colistin-carbapenem resistant isolate identified in this study lacked an mcr -type gene but revealed chromosomal mutations within pmrB , phoP , phoQ and pmrD genes. Some of the detected amino acid variations have previously been reported from colistin resistant E. coli isolates including PmrB D283G [ 25 ], PmrB G19R [ 26 ], PmrB H2R/ A360V, PhoP I44L, PhoQ L467M and PmrD N11D/M20K/A27T /K82Q/V83S [ 27 ]. More importantly we found that two CRE isolates belonging to ST167 and ST648 co-harbored 16S rRNA methyltransferase RmtB/RmtC and NDM-type carbapenemases.…”

Section: Discussionmentioning

confidence: 99%

Whole-genome sequence analysis of clinically isolated carbapenem resistant Escherichia coli from Iran

et al. 2023

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Background The emergence of carbapenem-resistant Enterobacterales (CRE) continues to threaten public health due to limited therapeutic options. In the current study the incidence of carbapenem resistance among the 104 clinical isolates of Escherichia coli and the genomic features of carbapenem resistant isolates were investigated. Methods The susceptibility to imipenem, tigecycline and colistin was tested by broth dilution method. Susceptibility to other classes of antimicrobials was examined by disk diffusion test. The presence of blaOXA-48, blaKPC, blaNDM, and blaVIM carbapenemase genes was examined by PCR. Molecular characteristics of carbapenem resistant isolates were further investigated by whole-genome sequencing (WGS) using Illumina and Nanopore platforms. Results Four isolates (3.8%) revealed imipenem MIC of ≥32 mg/L and positive results for modified carbapenem inactivation method and categorized as carbapenem resistant E. coli (CREC). Colistin, nitrofurantoin, fosfomycin, and tigecycline were the most active agents against all isolates (total susceptibility rate of 99, 99, 96 and 95.2% respectively) with the last three compounds being found as the most active antimicrobials for carbapenem resistant isolates (susceptibility rate of 100%). According to Multilocus Sequence Type (MLST) analysis the 4 CREC isolates belonged to ST167 (n = 2), ST361 (n = 1) and ST648 (n = 1). NDM was detected in all CREC isolates (NDM-1 (n = 1) and NMD-5 (n = 3)) among which one isolate co-harbored NDM-5 and OXA-181 carbapenemases. WGS further detected blaCTX-M-15, blaCMY-145, blaCMY-42 and blaTEM-1 (with different frequencies) among CREC isolates. Co-occurrence of NDM-type carbapenemase and 16S rRNA methyltransferase RmtB and RmtC was found in two isolates belonging to ST167 and ST648. A colistin-carbapenem resistant isolate which was mcr-negative, revealed various amino acid substitutions in PmrB, PmrD and PhoPQ proteins. Conclusion About 1.9% of E. coli isolates studied here were resistant to imipenem, colistin and/or amikacin which raises the concern about the outbreaks of difficult-to-treat infection by these emerging superbugs in the future.

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Section: Discussionmentioning

confidence: 99%

Whole-genome sequence analysis of clinically isolated carbapenem resistant Escherichia coli from Iran

et al. 2023

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PmrB Y358N, E123D amino acid substitutions are not associated with colistin resistance but with phylogeny in Escherichia coli

Butters,

Jovel,

Gow

et al. 2024

Microbiol Spectr

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Colistin resistance in Escherichia coli is of public health significance for its use to treat multidrug-resistant Gram-negative infections. Amino acid variations in PmrB have been implicated in colistin resistance in E. coli . In this cross-sectional study, 288 generic E. coli isolates from surveillance of broiler chicken and feedlot cattle feces, retail meat, wastewater, and well water were whole-genome sequenced. Phylogroup designation and screening for two amino acid substitutions in PmrB putatively linked to colistin resistance (Y358N, E123D) were performed in silico . Three additional data sets of publicly available E. coli assemblies were similarly scrutinized: (i) E. coli isolates from studies identifying the Y358N or E123D substitutions, (ii) colistin-susceptible E. coli isolates reported in the literature, and (iii) a random sampling of 14,700 E. coli assemblies available in the National Center for Biotechnology Information public database. Within all data sets, ≥95% of phylogroup B1 and C isolates have the PmrB Y358N variation. The PmrB E123D amino acid substitution was only identified in phylogroup B2 isolates, of which 94%–100% demonstrate the substitution. Both PmrB amino acid variations were infrequent in other phylogroups. Among published colistin susceptible isolates, colistin minimum inhibitory concentrations (MICs) were not higher in isolates bearing the E123D and Y358N amino acid variations than in isolates without these PmrB substitutions. The E123D and Y358N PmrB amino acid substitutions in E. coli appear strongly associated with phylogroup. The previously observed associations between Y358N and E123D amino acid substitutions in PmrB and colistin resistance in E. coli may be spurious. IMPORTANCE Colistin is a critical last-resort treatment for extensively drug-resistant Gram-negative infections in humans. Therefore, accurate identification of the genetic mechanisms of resistance to this antimicrobial is crucial to effectively monitor and mitigate the spread of resistance. Examining over 16,000 whole-genome sequenced Escherichia coli isolates, this study identifies that PmrB E123D and Y358N amino acid substitutions previously associated with colistin resistance in E. coli are strongly associated with phylogroup and are alone not sufficient to confer a colistin-resistant phenotype. This is a critical clarification, as both substitutions are identified as putative mechanisms of colistin resistance in many publications and a common bioinformatic tool. Given the potential spurious nature of initial associations of these substitutions with colistin resistance, this study's findings emphasize the importance of appropriate experimental design and consideration of relevant biological factors such as phylogroup when ascribing causal mechanisms of resistance to chromosomal variations.

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Sequence Duplication Within pmrB Gene Contribute to High-Level Colistin Resistance in Avian Pathogenic Escherichia coli

Cited by 2 publications

References 58 publications

Whole-genome sequence analysis of clinically isolated carbapenem resistant Escherichia coli from Iran

Whole-genome sequence analysis of clinically isolated carbapenem resistant Escherichia coli from Iran

PmrB Y358N, E123D amino acid substitutions are not associated with colistin resistance but with phylogeny in Escherichia coli

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