Comparative genomics and molecular epidemiology of colistin-resistant Acinetobacter baumannii

Jovana Kabic; Katarina Novovic; Dusan Kekic; Anika Trudic; Natasa Opavski; Ivica Dimkic; Branko Jovcic; Ina Gajic

doi:10.1016/j.csbj.2022.12.045

Comparative genomics and molecular epidemiology of colistin-resistant Acinetobacter baumannii

Comput Struct Biotechnol J. 2022 Dec 28:21:574-585. doi: 10.1016/j.csbj.2022.12.045. eCollection 2023.

Authors

Jovana Kabic¹, Katarina Novovic², Dusan Kekic¹, Anika Trudic^{3

4}, Natasa Opavski¹, Ivica Dimkic⁵, Branko Jovcic^{2

5}, Ina Gajic¹

Affiliations

¹ Institute of Microbiology and Immunology, Faculty of Medicine, University of Belgrade, 11000, Belgrade, Serbia.
² Laboratory for Molecular Microbiology, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, 11000, Belgrade, Serbia.
³ Department of Microbiology, Faculty of Medicine, University of Novi Sad, 21000, Novi Sad, Serbia.
⁴ Institute for Pulmonary Diseases of Vojvodina, 21204, Sremska Kamenica, Serbia.
⁵ Faculty of Biology, University of Belgrade, 11000, Belgrade, Serbia.

Abstract

This study aimed to investigate the prevalence and resistance mechanisms of colistin-resistant Acinetobacter baumannii (ColRAB) isolates in Serbia, assess their genetic relatedness to other circulating A. baumannii isolates in the neighbouring European countries, and analyse the global genomic epidemiology of ColRAB isolates. A total of 784 isolates of A. baumannii were recovered from hospitalised patients in Serbia between 2018 and 2021. The antimicrobial susceptibility testing was performed using disk diffusion and broth microdilution. All ColRAB isolates were subjected to DNA isolation and whole-genome sequencing (WGS). Overall, 3.94 % (n = 30) isolates were confirmed as ColRAB. Results of mutational and transcriptional analysis of genes associated with colistin resistance indicate the central role of the two-component regulating system, PmrAB, and increased expression of the pmrC gene in ColRAB. Most of the isolates (n = 29, 96.6 %) belonged to international clone II, with the most common sequence type being ST^Pas2 (n = 23, 76.6 %). Based on the WGS analysis, ColRAB isolates belonging to the same ST isolated in various countries were grouped into the same clusters, indicating the global dissemination of several high-risk clonal lineages. Phylogenomic analysis of ColRAB isolates, together with all previously published A. baumannii genomes from South-Eastern European countries, showed that colistin resistance arose independently in several clonal lineages. Comparative genomic analysis revealed multiple genes with various roles (transcriptional regulation, transmembrane transport, outer membrane assembly, etc.), which might be associated with colistin resistance in A. baumannii. The obtained findings serve as the basis for further studies, contributing to a better understanding of colistin resistance mechanisms in A. baumannii.

Keywords: Acinetobacter baumannii; Colistin resistance; Comparative genomics; Phylogenomics; WGS.