The evolution of colistin resistance increases bacterial resistance to host antimicrobial peptides and virulence

作者：Pramod K. Jangir, Lois Ogunlana, Petra Szili, Márton Simon Czikkely, Liam P. Shaw, Emily J. Stevens, Yang Yu, Qiue Yang, Yang Wang, Csaba Pál, Timothy R. Walsh, Craig MacLean · 发表于：eLife · 年份：2023 · DOI：10.7554/elife.84395 · 被引用次数：45 · 研究领域：Antibiotic Resistance in Bacteria、Antimicrobial Peptides and Activities、Vibrio bacteria research studies

Antimicrobial peptides (AMPs) offer a promising solution to the antibiotic resistance crisis. However, an unresolved serious concern is that the evolution of resistance to therapeutic AMPs may generate cross-resistance to host AMPs, compromising a cornerstone of the innate immune response. We systematically tested this hypothesis using globally disseminated mobile colistin resistance (MCR) that has been selected by the use of colistin in agriculture and medicine. Here, we show that MCR provides a selective advantage to Escherichia coli in the presence of key AMPs from humans and agricultural animals by increasing AMP resistance. Moreover, MCR promotes bacterial growth in human serum and increases virulence in a Galleria mellonella infection model. Our study shows how the anthropogenic use of AMPs can drive the accidental evolution of resistance to the innate immune system of humans and animals. These findings have major implications for the design and use of therapeutic AMPs and suggest that MCR may be difficult to eradicate, even if colistin use is withdrawn.