Abstract
BackgroundAcinetobacter baumannii is a multidrug-resistant (MDR) hazardous bacterium with very high antimicrobial resistance profiles. Outer membrane vesicles (OMVs) help directly and/or indirectly towards antibiotic resistance in these organisms. The present study aims to look on the proteomic profile of OMV as well as on the bacterial transcriptome upon exposure and induction with eravacycline, a new synthetic fluorocycline. RNA sequencing analysis of whole-cell and LC-MS/MS proteomic profiling of OMV proteome abundance were done to identify the differential expression among the eravacycline-induced A. baumannii ATCC 19606 and A. baumannii clinical strain JU0126.ResultsThe differentially expressed genes from the RNA sequencing were analysed using R package and bioinformatics software and tools. Genes encoding drug efflux and membrane transport were upregulated among the DEGs from both ATCC 19606 and JU0126 strains. As evident with the induction of eravacycline resistance, ribosomal proteins were upregulated in both the strains in the transcriptome profiles and also resistance pumps, such as MFS, RND, MATE and ABC transporters. High expression of stress and survival proteins were predominant in the OMVs proteome with ribosomal proteins, chaperons, OMPs OmpA, Omp38 upregulated in ATCC 19606 strain and ribosomal proteins, toluene tolerance protein, siderophore receptor and peptidases in the JU0126 strain. The induction of resistance to eravacycline was supported by the presence of upregulation of ribosomal proteins, resistance-conferring factors and stress proteins in both the strains of A. baumannii ATCC 19606 and JU0126, with the whole-cell gene transcriptome towards both resistance and stress genes while the OMVs proteome enriched more with survival proteins.ConclusionThe induction of resistance to eravacycline in the strains were evident with the increased expression of ribosomal and transcription related genes/proteins. Apart from this resistance-conferring efflux pumps, outer membrane proteins and stress-related proteins were also an essential part of the upregulated DEGs. However, the expression profiles of OMVs proteome in the study was independent with respect to the whole-cell RNA expression profiles with low to no correlation. This indicates the possible role of OMVs to be more of back-up additional protection to the existing bacterial cell defence during the antibacterial stress.
Highlights
Acinetobacter baumannii is a multidrug-resistant (MDR) hazardous bacterium with very high antimicrobial resistance profiles
Prior studies have reported many outer membrane protein (OMP) [31, 64] and resistance-conferring proteins expressed in Outer membrane vesicles (OMVs) of antibiotic-treated strains, our study identified many OMP and antibiotic resistancerelated proteins from both A. baumannii American Type Culture Collection (ATCC) 19606 and Jiangsu university strain No 0126 (JU0126)
The transcriptome of the whole cell and OMVs proteome abundance was studied for two A. baumannii strains, one an ATCC 19606 and a clinical isolate JU0126 strain in an eravacycline induced antibiotic resistant condition
Summary
Acinetobacter baumannii is a multidrug-resistant (MDR) hazardous bacterium with very high antimicrobial resistance profiles. Multidrug resistance (MDR) Acinetobacter baumannii is one of the most dangerous bacteria encountered among hospitalized and critically ill patients, infecting the immunosuppressed patients, who undergo invasive procedures and are treated with broad-spectrum antibiotics [1]. Infections, such as ventilator-associated pneumonia (VAP), urinary tract infections, bacteraemia, complicated skin and soft tissue, abdominal and central nervous system infections are commonly caused by A. baumannii [2]. Some strains are resistance to polymyxins—peptides making infected patient treatment more complicated and impossible in some cases leading to fatality [5, 6]
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