Pathogenic Lineage of <i>mcr</i>-Negative Colistin-Resistant <i>Escherichia coli</i>, Japan, 2008–2015

Sato, Toyotaka; Fukuda, Akira; Suzuki, Yuya; Shiraishi, Takeshi; Honda, Hiroyuki; Shinagawa, Morikazu; Yamamoto, Soh; Ogasawara, Nagahisa; Usui, Masaru; Takahashi, Hiroki; Takahashi, Satoshi; Tsutsumi, Yutaka; Yokota, Shinichi

doi:10.3201/eid2212.161117

Cited by 10 publications

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“…Detection of mcr genes and mutations in phoPQ and pmrAB in colistin-resistant E. coli isolates. In our previous study, we showed that the four colistin-resistant isolates do not possess mcr-1 and -2 (16). In the present study, we further examined the newly discovered mcr genes and found that mcr-3, -4, and -5 are also not harbored among the isolates.…”

Section: Resultsmentioning

confidence: 55%

“…The colistin-resistant O25b:H4-ST131-H30Rx (isolate SRE34), which has the highest reported colistin MIC (16 mg/liter), includes a deletion of 19 amino acid residues between positions 27 and 45 in PmrB, caused by a 57-bp deletion (between positions 79 and 135) in the pmrB gene. SRE44, another isolate of Serotype-sequence type and MIC for colistin (CST) and polymyxin B (PMB) were reported as described previously (16).…”

Section: Resultsmentioning

confidence: 99%

“…Bacterial isolates. Four colistin-resistant E. coli isolates comprising SRE34 and SRE44 (O25b:H4-ST131-H30Rx), SME222 (O25b:H4-ST131-H30R non-x), and SME296 (O18-ST416) derived from clinical specimens (urine catheter, urine catheter, indwelling pericardial drain, and urine, respectively) were used in this study (16). Ten colistin-susceptible E. coli isolates (nine O25b:H4-ST131-H30Rx or non-x isolates and E. coli ATCC 25922, with colistin MICs ranging from 0.125 to 0.5 mg/liter) were used as reference strains.…”

Section: Methodsmentioning

confidence: 99%

“…In our previous study, we reported the isolation from clinical specimens of colistinresistant E. coli O25b:H4-ST131-H30Rx and non-x isolates lacking the mcr-1 and mcr-2 genes (2.2% of all ST131 isolates) (16). This indicated the presence of a colistin-resistant population in the ST131 lineage.…”

mentioning

confidence: 89%

“…Therefore, a better understanding of colistin resistance in ST131 could prove valuable for treatment and prevention. Interestingly, the patients from whom colistin-resistant E. coli strains were isolated in our previous study (16) had no history of colistin or polymyxin B therapy. This indicates the possibility that these E. coli isolates can colonize in patients in the absence of colistin selection pressure and without loss of bacterial fitness due to the acquisition of colistin resistance.…”

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confidence: 95%

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Contribution of Novel Amino Acid Alterations in PmrA or PmrB to Colistin Resistance in mcr -Negative Escherichia coli Clinical Isolates, Including Major Multidrug-Resistant Lineages O25b:H4-ST131- H 30Rx and Non-x

Sato

Shiraishi

Hiyama

et al. 2018

Antimicrob Agents Chemother

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Colistin is a last-line drug for multidrug-resistant Gram-negative bacteria. We previously reported four plasmid-mediated colistin resistance () gene-negative colistin-resistant clinical isolates, including the major pathogenic and fluoroquinolone-resistant strains O25b:H4-ST131-30Rx (isolates SRE34 and SRE44; MIC for colistin = 16 mg/liter), non-x (SME296; MIC = 8 mg/liter), and O18-ST416 (SME222; MIC = 4 mg/liter). In this study, we investigated the colistin resistance mechanism and identified novel amino acid substitutions or deletions in the PmrAB two-component system that activates (encoding a phosphoethanolamine transferase) and (encoding an undecaprenyl phosphate-alpha-4-amino-4-deoxy-l-arabinose arabinosyl transferase) in all colistin-resistant isolates. SRE34 possessed deletion Δ27-45 (LISVFWLWHESTEQIQLFE) in PmrB, SRE44 possessed substitution L105P in PmrA, and both SME222 and SME296 included substitution G206D in PmrB. Matrix-assisted laser desorption ionization-time of flight mass spectrometry revealed that lipid A is modified with phosphoethanolamine in all four isolates. Deletion of decreased colistin MICs to 0.5 mg/liter and lowered and expression. Chromosomal replacement of mutated or in colistin-susceptible O25b:H4-ST131 strain SME98 (colistin MIC = 0.5 mg/liter) increased the colistin MIC to that of the respective parent colistin-resistant isolate. In addition, SME98 mutants in which was replaced with mutated showed no significant differences in bacterial growth and competition culture from the parent strain, except for the mutant with L105P in PmrA, whose growth was significantly suppressed in the presence of the parent strain. In conclusion, some O25b:H4-ST131 strains appear to acquire colistin resistance via phosphoethanolamine modification of lipid A through amino acid changes in PmrAB, and the amino acid changes in PmrB do not influence bacterial growth.

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Section: Resultsmentioning

confidence: 55%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 89%

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confidence: 95%

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