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<p>Plasmids carrying the mobilized colistin-resistance gene <i>mcr-1</i> are prevalent among multidrug-resistant Gram-negative pathogens, yet their broad impact on bacterial physiology and virulence remains unclear. Here, we demonstrate that acquisition of an <i>mcr-1</i> plasmid concurrently increases antimicrobial resistance and pathogenicity in <i>Escherichia coli</i>. On the same plasmid, the XRE-family transcriptional regulator EcaR cooperates with MCR-1 to activate the <i>wec</i> operon, driving biosynthesis of two surface polysaccharides: enterobacterial common antigen (ECA) and a high-molecular-weight O-chain. Expression of these surface polysaccharides increases bile resistance and virulence in a murine model and further elevates colistin resistance. MCR-1 enhances transcription of upstream genes in the <i>wec</i> operon, whereas EcaR directly activates an internal promoter (P<sub><i>wecE</i></sub>) to induce downstream gene expression. Thus, both components are required for surface polysaccharide expression, and deletion of either abolishes the phenotype. Genomic analysis of publicly available <i>mcr</i> plasmids reveals widespread co-occurrence of <i>mcr-1</i> and <i>ecaR</i> on IncI2 and IncX4 plasmids, indicating their functional complementarity. These findings uncover a mechanism by which resistance plasmids remodel the bacterial surface, linking horizontal gene transfer to coordinated regulation of antimicrobial resistance and virulence.</p>

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Colistin resistance plasmids dually enhance bacterial virulence and antibiotic resistance via surface polysaccharide biosynthesis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月12日

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  • Eunbyeol Ahn,
  • Jinshil Kim,
  • Junyao Jiang,
  • Joonbeom Kim,
  • Artur Muszyński,
  • Katarzyna Kasperkiewicz,
  • Hojun Shin,
  • Yingqi Cao,
  • Yejin Soh,
  • Youngjae Park,
  • Christian Heiss,
  • Liyanage Devthilini Pasasum Fernando,
  • Parastoo Azadi,
  • Yang Wang,
  • Byeonghwa Jeon,
  • Sangryeol Ryu

摘要

Plasmids carrying the mobilized colistin-resistance gene mcr-1 are prevalent among multidrug-resistant Gram-negative pathogens, yet their broad impact on bacterial physiology and virulence remains unclear. Here, we demonstrate that acquisition of an mcr-1 plasmid concurrently increases antimicrobial resistance and pathogenicity in Escherichia coli. On the same plasmid, the XRE-family transcriptional regulator EcaR cooperates with MCR-1 to activate the wec operon, driving biosynthesis of two surface polysaccharides: enterobacterial common antigen (ECA) and a high-molecular-weight O-chain. Expression of these surface polysaccharides increases bile resistance and virulence in a murine model and further elevates colistin resistance. MCR-1 enhances transcription of upstream genes in the wec operon, whereas EcaR directly activates an internal promoter (PwecE) to induce downstream gene expression. Thus, both components are required for surface polysaccharide expression, and deletion of either abolishes the phenotype. Genomic analysis of publicly available mcr plasmids reveals widespread co-occurrence of mcr-1 and ecaR on IncI2 and IncX4 plasmids, indicating their functional complementarity. These findings uncover a mechanism by which resistance plasmids remodel the bacterial surface, linking horizontal gene transfer to coordinated regulation of antimicrobial resistance and virulence.