A novel decoy strategy for polymyxin resistance in Acinetobacter baumannii

eLife

Tae Kwon Lee¹  Woojun Park²  Misung Kim²  Jaeeun Park²  Jihye Yang²  Bora Shin²  Mingyeong Kang² 

[1] Department of Environmental Engineering, Yonsei University, Wonju, Republic of Korea;Laboratory of Molecular Environmental Microbiology, Department of Environmental Science and Ecological Engineering, Korea University, Seoul, Republic of Korea;

关键词: acinetobacter baumannii;    lps modifications;    outer membrane vesicl;    component regulatory systems;    experimental evolution;    polymyxin resistance;    Other;   

DOI  :  10.7554/eLife.66988

来源: eLife Sciences Publications, Ltd

【 摘 要 】

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.

【 授权许可】

CC BY