biostudies-literatureSato TJSPS KAKENHIThe Food Safety Commission of JapanGSK Japan Research Grant 2016Yuasa Memorial Fundatione00864-18https://www.ebi.ac.uk/biostudies/studies/S-EPMC6125499biostudies-literatureUnknown62(9)Colistin is a last-line drug for multidrug-resistant Gram-negative bacteria. We previously reported four plasmid-mediated colistin resistance (<i>mcr</i>) gene-negative colistin-resistant <i>Escherichia coli</i> clinical isolates, including the major pathogenic and fluoroquinolone-resistant strains O25b:H4-ST131-<i>H</i>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 <i>eptA</i> (encoding a phosphoethanolamine transferase) and <i>arnT</i> (encoding an undecaprenyl phosphate-alpha-4-amino-4-deoxy-l-arabinose arabinosyl transferasAntimicrobial agents and chemotherapyContribution of Novel Amino Acid Alterations in PmrA or PmrB to Colistin Resistance in <i>mcr</i>-Negative Escherichia coli Clinical Isolates, Including Major Multidrug-Resistant Lineages O25b:H4-ST131-<i>H</i>30Rx and Non-x.PMC612549917K156881703Shiraishi TKuronuma KHiyama YSato TShinagawa MTakahashi SUsui MTamura YMasumori NHonda HYokota SIfalseContribution of Novel Amino Acid Alterations in PmrA or PmrB to Colistin Resistance in <i>mcr</i>-Negative Escherichia coli Clinical Isolates, Including Major Multidrug-Resistant Lineages O25b:H4-ST131-<i>H</i>30Rx and Non-x.Colistin is a last-line drug for multidrug-resistant Gram-negative bacteria. We previously reported four plasmid-mediated colistin resistance (<i>mcr</i>) gene-negative colistin-resistant <i>Escherichia coli</i> clinical isolates, including the major pathogenic and fluoroquinolone-resistant strains O25b:H4-ST131-<i>H</i>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 <i>eptA</i> (encoding a phosphoethanolamine transferase) and <i>arnT</i> (encoding an undecaprenyl phosphate-alpha-4-amino-4-deoxy-l-arabinose arabinosyl transferas2018-01-01T00:00:00Z2018 Sep2026-04-14T19:06:29.438Z2019-06-06T20:07:27ZS-EPMC61254992991495210.1128/AAC.00864-1810.1128/aac.00864-18