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

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 () and Sangryeol Ryu ()
Additional contact information
Eunbyeol Ahn: Seoul National University
Jinshil Kim: Seoul National University
Junyao Jiang: China Agricultural University
Joonbeom Kim: Seoul National University
Artur Muszyński: University of Georgia
Katarzyna Kasperkiewicz: University of Silesia
Hojun Shin: Seoul National University
Yingqi Cao: China Agricultural University
Yejin Soh: Seoul National University
Youngjae Park: Seoul National University
Christian Heiss: University of Georgia
Liyanage Devthilini Pasasum Fernando: University of Georgia
Parastoo Azadi: University of Georgia
Yang Wang: China Agricultural University
Byeonghwa Jeon: University of Minnesota
Sangryeol Ryu: Seoul National University

Nature Communications, 2025, vol. 16, issue 1, 1-17

Abstract: Abstract 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.

Date: 2025
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DOI: 10.1038/s41467-025-65412-9

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