A novel decoy strategy for polymyxin resistance in <i>Acinetobacter baumannii</i>.

Abstract

Modification of the outer membrane charge by a polymyxin B (PMB)-induced PmrAB two-component system appears to be a dominant phenomenon in PMB-resistant <i>Acinetobacter baumannii</i>. PMB-resistant variants and many clinical isolates also appeared to produce outer membrane vesicles (OMVs). Genomic, transcriptomic, and proteomic analyses revealed that upregulation of the <i>pmr</i> operon and decreased membrane-linkage proteins (OmpA, OmpW, and BamE) are linked to overproduction of OMVs, which also promoted enhanced biofilm formation. The addition of OMVs from PMB-resistant variants into the cultures of PMB-susceptible <i>A. baumannii</i> and the clinical isolates protected these susceptible bacteria from PMB. Taxonomic profiling of in vitro human gut microbiomes under anaerobic conditions demonstrated that OMVs completely protected the microbial community against PMB treatment. A <i>Galleria mellonella-</i>infection model with PMB treatment showed that OMVs increased the mortality rate of larvae by protecting <i>A. baumannii</i> from PMB. Taken together, OMVs released from <i>A. baumannii</i> functioned as decoys against PMB.