Whole Genome Analysis of Extensively Drug-Resistant Acinetobacter baumannii Clinical Isolates in Thailand

Abstract

Background: Acinetobacter baumannii is recognized as a majority opportunistic nosocomial pathogen causing hospital-acquired infection worldwide. The increasing prevalence of extensively drug-resistant Acinetobacter baumannii (XDRAB) has become a rising concern in healthcare facilities and has impeded public health due to limitation of therapeutic options and are associated with high morbidity and mortality as well as longer hospitalization. Whole-genome sequencing of highly multidrug resistant A. baumannii will increase the understanding of resistant mechanisms, the emergence of novel resistance, genetic relationships among the isolates, source tracking, and treatment decisions in selected patients.

Objective: This study revealed the genomic analysis to explore blaOXA-23 harboring XDRAB isolates in Thailand.

Methods: Whole-genome sequencing of the two XDRAB isolates was carried out on a HiSeq2000 Illumina platform and susceptibility on antimicrobials was conducted.

Results: Both isolates revealed sequence types of international, clone II-carrying, multiple antimicrobial- resistant genes-ST195 and ST451. They were resistant to antimicrobial agents in all drug classes tested for Acinetobacter spp. They carried 18 antimicrobial-resistant genes comprising of 4 β-lactamase genes (blaOXA-23, blaOXA-66, blaTEM-1D, blaADC-25), 4 aminoglycoside-resistant genes (armA, aph(3')-Ia, aph(3")-Ib, aph(6)-Id), 3 macrolide-resistant genes (amvA, mphE, msrE), 1 sulfonamide- resistant gene (sul-2), 2 tetracycline-resistant genes (tetB, tetR), 1 resistant-nodulation-cell division (RND) antibiotic efflux pump gene cluster, 2 major facilitator superfamily (MFS) antibiotic efflux pump genes (abaF, abaQ), and 1 small multidrug-resistant (SMR) antibiotic efflux pump gene (abeS). Mutation of gyrA (S81L) occurred in both isolates.

Conclusion: Whole-genome sequencing revealed both blaOXA-23 harboring XDRAB isolates were clustered under international clone II with different STs and carrying multiple antimicrobial-resistant genes conferred their resistance to antimicrobial agents. Inactivation of antimicrobials and target modification by enzymes and pumping antibiotics by efflux pump are mainly resistance mechanism of the XDRAB in this study.

Keywords: Acinetobacter baumannii; Thailand; XDRAB.; carbapenem-resistance; extensively-drug resistance; whole-genome sequencing.