Department of Biology, University of Oxford, Oxford, United Kingdom
Lois Ogunlana
Department of Biology, University of Oxford, Oxford, United Kingdom
Petra Szili
Synthetic and Systems Biology Unit, Biological Research Centre, Eötvös Loránd Research Network, Szeged, Hungary; Doctoral School of Multidisciplinary Medical Sciences, University of Szeged, Szeged, Hungary
Marton Czikkely
Synthetic and Systems Biology Unit, Biological Research Centre, Eötvös Loránd Research Network, Szeged, Hungary
Liam P Shaw
Department of Biology, University of Oxford, Oxford, United Kingdom
Emily J Stevens
Department of Biology, University of Oxford, Oxford, United Kingdom
Yang Yu
Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, South China Agricultural University, Guangzhou, China
Qiue Yang
Fujian Provincial Key Laboratory of Soil Environmental Health and RegulaWon, College of Resources and Environment, Fujian Agriculture and Forestry University, Fuzhou, China
Yang Wang
Beijing Advanced Innovation Centre for Food Nutrition and Human Health, College of Veterinary Medicine, China Agricultural University, Beijing, China
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for the design and use of therapeutic AMPs and suggest that MCR may be difficult to eradicate, even if colistin use is withdrawn.
