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

Jangir, Pramod; Ogunlana, Lois; Szili, Petra; Czikkely, Marton; P Shaw, Liam; Stevens, Emily J; Yu, Yang; Yang, Qiue; Wang, Yang; Pal, Csaba; R Walsh, Timothy; R MacLean, Craig

doi:10.7554/elife.84395

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

Jangir, Pramod; Ogunlana, Lois; Szili, Petra; Czikkely, Marton; P Shaw, Liam; Stevens, Emily J; Yu, Yang; Yang, Qiue; Wang, Yang; Pal, Csaba; R Walsh, Timothy; R MacLean, Craig

Authors

Pramod Jangir

Lois Ogunlana

Petra Szili

Marton Czikkely

Liam P Shaw

Dr Emily Belcher e.j.stevens@keele.ac.uk

Yang Yu

Qiue Yang

Yang Wang

Csaba Pal

Timothy R Walsh

Craig R MacLean

Abstract

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for the design and use of therapeutic AMPs and suggest that MCR may be difficult to eradicate, even if colistin use is withdrawn.

Citation

Jangir, P., Ogunlana, L., Szili, P., Czikkely, M., P Shaw, L., Stevens, E. J., …R MacLean, C. (2023). The evolution of colistin resistance increases bacterial resistance to host antimicrobial peptides and virulence. eLife, 12, 1-22. https://doi.org/10.7554/elife.84395

Journal Article Type	Article
Acceptance Date	Apr 5, 2023
Publication Date	Apr 25, 2023
Deposit Date	Feb 26, 2024
Journal	eLife
Print ISSN	2050-084X
Electronic ISSN	2050-084X
Publisher	eLife Sciences Publications
Peer Reviewed	Peer Reviewed
Volume	12
Article Number	e84395
Pages	1-22
DOI	https://doi.org/10.7554/elife.84395
Publisher URL	https://elifesciences.org/articles/84395