Fitness Costs of Tigecycline Resistance in Acinetobacter baumannii and the Resistance Mechanism Revealed by a Transposon Mutation Library

Abstract

Acinetobacter baumannii is one of the main pathogens causing nosocomial and community-acquired infections. Tigecycline is an important antibiotic for the treatment of multidrug-resistant A. baumannii infections, but strains resistant to tigecycline have also emerged. There are still many unclear questions concerning the mechanism of tigecycline resistance in A. baumannii. In this study, tigecycline-susceptible and tigecycline-intermediate strains were gradually cultured with sub-minimum inhibitory concentrations of tigecycline to select for tigecycline-resistant mutants, and a tigecycline-resistant strain was cultured under 42 °C to select for tigecycline-susceptible mutants. We found that the acquisition of tigecycline resistance affected the susceptibility of the strains to other antibiotics. Resistance to ampicillin–sulbactam is negatively correlated with tigecycline resistance. The strains will experience fitness costs along with the acquisition of tigecycline resistance. Tigecycline resistance in the strains was not related to 16S rRNA target variation or outer membrane integrity alteration. By constructing a transposon mutation library, we found that transposon insertion of the adeL gene reduced the sensitivity of A. baumannii to tigecycline. This study provides important clues for understanding the mechanism of tigecycline resistance in A. baumannii.

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

“…Both the CUS (chaperon-usher secretion) operator system and the surface antigen protein A are related to the formation of biofilms [35,36]. In this study, these biofilm formation-related proteins CsuA/B, CsuC, CsuE were all up-regulated in 17978R, but down-regulated in A54R, which was consistent with the results of the biofilm-forming ability of the two strains [37]. The relationship between the biofilm-forming ability and antibiotic resistance is still controversial.…”

Molecular mechanisms of tigecycline-resistance among Enterobacterales

“…Specifically, the presence of multi-drug resistant (MDR) pathogens raises a noteworthy concern. MDR strains often occurring in intensive care units have shown an alarming mortality rate due to the difficulty of treatment with antibiotics ( Wang P. et al., 2022 ). According to susceptibility levels in the Asia-Western Pacific region, tigecycline treatment is currently effective in most MDR infections ( Li et al., 2015 ).…”

“…Notably mcr-1 plasmids can act as helper plasmids, potentially enhancing the chance of dissemination of plasmid-mediated tigecycline resistance ( Sun J. et al., 2019 ). Various studies revealed the spread of genes through HGT ( Wang P. et al., 2022 ). Tet genes can be found in plasmids harboring IncQ1.…”