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<p>The global dissemination of mobile colistin resistance (<i>mcr</i>) genes represents a significant public health threat due to colistin’s critical role in treating multidrug-resistant (MDR) bacterial infections. We identified high rates of carbapenem resistance in <i>Escherichia coli</i> (27.82%) and <i>Klebsiella pneumoniae</i> (57.98%) and colistin resistance in <i>E. coli</i> (7.52%) and <i>K. pneumoniae</i> (19.68%) among MDR clinical isolates in Thailand. We reported sequences of self-transferable IncX4 plasmids (~ 34&#xa0;kb) that facilitated the spread of the <i>mcr-1.1</i> gene among six diverse MDR strains, often co-transferring <i>bla</i><sub>CTX-M-55</sub>. Additionally, <i>E. coli</i> ST101 was found to co-transfer <i>mcr-1.1</i>, <i>mcr-3.5</i>, <i>bla</i><sub>CTX-M-55</sub>, and <i>tet</i>(X4) via three plasmids (~ 34-kb IncX4, ~ 84-kb IncFII, ~ 278-kb IncHI2), resulting in increases in MICs for colistin, ceftriaxone, and tigecycline. Core SNP analysis revealed that closely related IncX4 plasmids harbouring <i>mcr-1</i> (&lt; 35 SNP differences) were reported from at least 12 countries. We first demonstrated the inhibitory effects of benzyl isothiocyanate (BITC) on the conjugation of <i>mcr-1</i>-bearing IncX4 plasmids to 1.57 ± 1.00% to 48.86 ± 12.31% relative to control (100%), targeting VirB4 and VirB11 proteins, reducing ATPase activity by over 30%. This study highlights the widespread <i>mcr-1</i>-harbouring IncX4 plasmids and proposes BITC as a potential inhibitor to control the dissemination of colistin resistance.</p>

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Inhibitory effects of benzyl isothiocyanate on widespread mcr-1-harbouring IncX4 plasmid transfer

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年4月15日

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  • Sirirat Luk-In,
  • Kamonrat Phopin,
  • Sasina Bangmuangngam,
  • Tanittha Chatsuwan,
  • Dhammika Leshan Wannigama,
  • Aye Mya Sithu Shein,
  • Rongpong Plongla,
  • Ratana Lawung,
  • Sakda Yainoy,
  • Warawan Eiamphungporn,
  • Chawalit Chatupheeraphat,
  • Tanawut Tantimongcolwat

摘要

The global dissemination of mobile colistin resistance (mcr) genes represents a significant public health threat due to colistin’s critical role in treating multidrug-resistant (MDR) bacterial infections. We identified high rates of carbapenem resistance in Escherichia coli (27.82%) and Klebsiella pneumoniae (57.98%) and colistin resistance in E. coli (7.52%) and K. pneumoniae (19.68%) among MDR clinical isolates in Thailand. We reported sequences of self-transferable IncX4 plasmids (~ 34 kb) that facilitated the spread of the mcr-1.1 gene among six diverse MDR strains, often co-transferring blaCTX-M-55. Additionally, E. coli ST101 was found to co-transfer mcr-1.1, mcr-3.5, blaCTX-M-55, and tet(X4) via three plasmids (~ 34-kb IncX4, ~ 84-kb IncFII, ~ 278-kb IncHI2), resulting in increases in MICs for colistin, ceftriaxone, and tigecycline. Core SNP analysis revealed that closely related IncX4 plasmids harbouring mcr-1 (< 35 SNP differences) were reported from at least 12 countries. We first demonstrated the inhibitory effects of benzyl isothiocyanate (BITC) on the conjugation of mcr-1-bearing IncX4 plasmids to 1.57 ± 1.00% to 48.86 ± 12.31% relative to control (100%), targeting VirB4 and VirB11 proteins, reducing ATPase activity by over 30%. This study highlights the widespread mcr-1-harbouring IncX4 plasmids and proposes BITC as a potential inhibitor to control the dissemination of colistin resistance.