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.
Keywords: acinetobacter baumannii; component regulatory systems; experimental evolution; infectious disease; lps modifications; microbiology; outer membrane vesicl; polymyxin resistance.
Wrapped in a thick, protective outer membrane, Acinetobacter baumannii bacteria can sometimes cause serious infections when they find their way into human lungs and urinary tracts. Antibiotics are increasingly ineffective against this threat, which forces physicians to resort to polymyxin B, an old, positively-charged drug that ‘sticks’ to the negatively-charged proteins and fatty components at the surface of A. baumannii. 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. In fact, this protective effect extended to other species, shielding whole communities of bacteria against polymyxin B. In vivo, the vesicles protected bacteria in moth larvae infected with A. baumannii, leading to a higher death rate in the animals. Experiments showed that the negatively-charged vesicles worked as decoys, trapping the positively-charged polymyxin B away from its target. Taken together, the findings by Park et al. highlight a new strategy that allows certain strains of bacteria to protect themselves from antibiotics, while also benefitting the rest of the microbial community.
© 2021, Park et al.