RT Journal Article
SR Electronic
T1 The evolution of colistin resistance increases bacterial resistance to host antimicrobial peptides and virulence
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.02.12.480185
DO 10.1101/2022.02.12.480185
A1 Pramod K. Jangir
A1 Lois Ogunlana
A1 Petra Szili
A1 Márton Czikkely
A1 Emily J. Stevens
A1 Yu Yang
A1 Qiue Yang
A1 Yang Wang
A1 Csaba Pál
A1 Timothy R. Walsh
A1 Craig MacLean
YR 2022
UL http://biorxiv.org/content/early/2022/02/12/2022.02.12.480185.abstract
AB 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 E. 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design and use of therapeutic AMPs and they suggest that MCR will be difficult to eradicate, even if colistin use is withdrawn.Competing Interest StatementThe authors have declared no competing interest.