The Mechanism of Tigecycline Resistance in Acinetobacter baumannii Revealed by Proteomic and Genomic Analysis.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, [2000-

Anti-Bacterial Agents*/pharmacology ; Anti-Bacterial Agents*/metabolism ; Acinetobacter baumannii*/metabolism; Tigecycline/pharmacology ; Proteomics ; Plasmids ; Microbial Sensitivity Tests ; Drug Resistance, Multiple, Bacterial ; Bacterial Proteins/genetics ; Bacterial Proteins/metabolism

The mechanism of tigecycline resistance in A. baumannii remains largely unclear. In this study, we selected a tigecycline-resistant and a tigecycline-susceptible strain from a tigecycline-susceptible and a resistant strain, respectively. Proteomic and genomic analyses were performed to elucidate the variations associated with tigecycline resistance. Our study showed proteins associated with efflux pump, biofilm formation, iron acquisition, stress response, and metabolic ability are upregulated in tigecycline resistant strains, and efflux pump should be the key mechanism for tigecycline resistance. By genomic analysis, we found several changes in the genome that can explain the increased level of efflux pump, including the loss of the global negative regulator hns in the plasmid and the disruption of the hns gene and acrR gene on the chromosome by the insertion of IS5. Collectively, we not only revealed the phenomenon that the efflux pump is mainly responsible for tigecycline resistance, but also highlighted the mechanism at the genomic level, which will help in understanding the resistance mechanism in detail and provide clues for the treatment of clinical multiple drug-resistant A. baumannii .

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NSFC81572041 National Natural Science Foundation of China

Keywords: Acinetobacter baumannii; insertion sequence; proteome; tigecycline resistance; whole genome sequencing

70JE2N95KR (Tigecycline)
0 (Anti-Bacterial Agents)
0 (Bacterial Proteins)

Date Created: 20230527 Date Completed: 20230529 Latest Revision: 20230529

20230529

PMC10218405

10.3390/ijms24108652

37239993