A novel decoy strategy for polymyxin resistance in Acinetobacter baumannii.

Jaeeun Park,Tae Kwon Lee,Jihye Yang,Woojun Park,Mingyeong Kang,Bora Shin,Misung Kim

doi:10.7554/elife.66988

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 Acinetobacter baumannii. 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 pmr 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 A. baumannii 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 Galleria mellonella-infection model with PMB treatment showed that OMVs increased the mortality rate of larvae by protecting A. baumannii from PMB. Taken together, OMVs released from A. baumannii functioned as decoys against PMB.

Highlights

Pathogenic Acinetobacter baumannii strains cause urinary tract infections and ventilator-associated pneumonia (Wright et al, 2014)
outer membrane vesicles (OMVs) biogenesis was thought to be linked to the elevated hydrophobicity of the cell surface in P. putida, which caused greater biofilm formation (Baumgarten et al, 2012)
The OMVs produced by A. baumannii have been shown to have a virulence factor (OmpA) and an antibiotic-resistance factor (AmpC) (Weber et al, 2017)

Summary

Introduction

Pathogenic Acinetobacter baumannii strains cause urinary tract infections and ventilator-associated pneumonia (Wright et al, 2014). Scientists have noticed that when bacteria are exposed to lethal drugs, they often react by releasing vesicles, small ‘sacs’ made of pieces of the outer membranes which can contain DNA or enzymes How this strategy protects the cells against antibiotics such as polymyxin B remains poorly understood. To investigate this question, Park et al examined different strains of A. baumannii, showing that bacteria resistant to polymyxin B had lower levels of outer membrane proteins but would release more vesicles. Adding vesicles from resistant strains to non-resistant A. baumannii cultures helped cells to survive the drugs This protective effect extended to other species, shielding whole communities of bacteria against polymyxin B. These vesicles can protect the OMV producer, and the entire bacterial community from the bactericidal effects of PMB

Results

Discussion

Materials and methods