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Genomic investigation unveils colistin resistance mechanism in carbapenem-resistant Acinetobacter baumannii clinical isolates

Saranya Vijayakumar, Rayapadi G. Swetha, Yamuna Devi Bakthavatchalam, Karthick Vasudevan, Baby Abirami Shankar, Agilandeeswari Kirubananthan, Kāmini Walia, Sudha Ramaiah et al.

Microbiology Spectrum, 2024

29 citations

Abstract

ABSTRACT Colistin resistance in Acinetobacter baumannii is mediated by multiple mechanisms. Recently, mutations within pmrABC two-component system and overexpression of eptA gene due to upstream insertion of IS Aba1 have been shown to play a major role. Thus, the aim of our study is to characterize colistin resistance mechanisms among the clinical isolates of A. baumannii in India. A total of 207 clinical isolates of A. baumannii collected from 2016 to 2019 were included in this study. Mutations within lipid A biosynthesis and pmrABC genes were characterized by whole-genome shotgun sequencing. Twenty-eight complete genomes were further characterized by hybrid assembly approach to study insertional inactivation of lpx genes and the association of IS Aba1-eptA . Several single point mutations (SNPs), like M12I in pmrA , A138T and A444V in pmrB , and E117K in lpxD, were identified. We are the first to report two novel SNPs (T7I and V383I) in the pmrC gene. Among the five colistin-resistant A. baumannii isolates where complete genome was available, the analysis showed that three of the five isolates had IS Aba1 insertion upstream of eptA . No mcr genes were identified among the isolates. We mapped the SNPs on the respective protein structures to understand the effect on the protein activity. We found that majority of the SNPs had little effect on the putative protein function; however, some SNPs might destabilize the local structure. Our study highlights the diversity of…

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