Correlation of RND efflux pump expression and AdeRS mutations in tigecycline-resistant Acinetobacter baumannii from Thai clinical isolates

Abstract

Tigecycline-resistant Acinetobacter baumannii (TRAB) is increasing in Thailand, complicating antibiotic treatment due to limited antibiotic options. The specific resistance mechanism behind tigecycline resistance is still unclear, necessitating further investigation. We investigated the presence of OXA-type carbapenemases, the antimicrobial susceptibility profile, the inhibitory effect of carbonyl cyanide m-chlorophenylhydrazone (CCCP) on tigecycline susceptibility, the expression levels of RND-type efflux pumps and amino acid substitutions within a two-component regulatory system on 30 Thai clinical isolates. Our investigation revealed that most of (73.3%) TRAB isolates expressed at least one member of the Ade efflux pumps. The adeB was most frequently expressed (63.3%), followed by adeR (50%), adeS (43.3%), adeJ (30%) and adeG (10%). Overexpression of the AdeABC was associated with increased tigecycline minimum inhibitory concentrations (MICs) and amino acid substitutions within the AdeRS. Notably, isolates harbouring simultaneous mutations in these genes exhibited an increase in the transcription level of the adeB. Our findings highlight the significant role of the AdeABC system in tigecycline resistance among Thai clinical TRAB isolates. This is supported by point mutations within the AdeRS and upregulated expression of the adeB. These results provide valuable insights for understanding resistance mechanisms and developing novel therapeutic strategies.