Cross resistance emergence to polymyxins in Acinetobacter baumannii exposed in vitro to an antimicrobial peptide

Abstract

Multidrug-resistant bacteria are a growing public health concern. Antimicrobial peptides (AMPs) are proposed alternatives to classical antibiotics towards infections caused by resistant bacteria. TAT-RasGAP 317-326 is an AMP able to target Gram-negative bacteria and is especially efficient towards Acinetobacter baumannii . In this study, we performed in vitro resistance selection on several A. baumannii strains, in order to determine to which extent these bacteria can develop resistance to TAT-RasGAP 317-326 . A. baumannii rapidly developed resistance to TAT-RasGAP 317-326 and subsequently, in approximately half of the cases, cross-resistance to last-resort polypeptidic antibiotics polymyxins. Cross-resistant isolates predominantly bore mutations in the pmrAB operon, involved in modulation of lipopolysaccharides' charge at the bacterial surface, similarly to polymyxin-resistant clinical isolates. We thus show here that contact of A. baumannii with an AMP structurally different from polymyxins can induce unexpected cross-resistance towards them. This indicates that precautions must be taken for the clinical application of AMPs.