Abstract

Acinetobacter baumannii has emerged as one of the dominant nosocomial human pathogens associated with high morbidity and mortality globally. Increased incidences of carbapenem-resistant A. baumannii (CRAB) have resulted in an enormous socioeconomic burden on health-care systems. Here, we report the genotypic and phenotypic characterization of novel ST1816 and ST128 variants in A. baumannii strains belonging to International clone II (GC2) with capsule types KL1:OCL8 and KL3:OCL1d from India. Sequence analysis revealed the presence of diverse virulome and resistome in these clinical strains, in addition to islands, prophages, and resistance genes. The oxacillinase blaOXA–23detected in the genomic island also highlighted the coexistence of blaOXA–66/blaOXA–98, blaADC73/blaADC–3, and blaTEM–1D in their mobile scaffolds, which is alarming. Together with these resistance-determining enzymes, multidrug efflux transporters also harbored substitutions, with increased expression in CRAB strains. The hotspot mutations in colistin resistance-conferring operons, PmrAB, LpxACD, and AdeRS, were additionally confirmed. Phenotype microarray analysis indicated that multidrug-resistant strains A. baumannii DR2 and A. baumannii AB067 preferred a range of antimicrobial compounds as their substrates relative to the other. To our knowledge, this is the first comprehensive report on the characterization of A. baumannii variants ST1816 and ST128, with different genetic makeup and genome organization. The occurrence of CRAB infections worldwide is a severe threat to available limited therapeutic options; hence, continued surveillance to monitor the emergence and dissemination of such novel ST variants in A. baumannii is imperative.

Highlights

  • Antimicrobial resistance (AMR) is a primary public health concern across humans, plants, animals, and environmental sectors and is the recognized determinant for therapeutic failure resulting in high morbidity and mortality worldwide

  • The genome reads of A. baumannii strain DR2 assembled (GCA_002265675.1) into a single chromosome of size 3,897,527 Mb, having 39.0% G + C content; the number of contigs being 102, with N50 157,362 bp, L50 as 10 (Genbank accession number NOXO01), and A. baumannii strain DR2 consisted of 3,810 genes, 3,737 CDS, 3,668 coding genes, 73 RNA genes, 63 tRNAs, and 69 pseudogenes

  • The World Health Organization (WHO) has ranked carbapenem-resistant A. baumannii (CRAB) among its “top critical threat” pathogens, and outbreak clones usually belong to the international clonal groups I, II, and III

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Summary

Introduction

Antimicrobial resistance (AMR) is a primary public health concern across humans, plants, animals, and environmental sectors and is the recognized determinant for therapeutic failure resulting in high morbidity and mortality worldwide. In May 2015, the World Health Organization (WHO) published its national action plan, emphasizing global health governance by improving awareness, strengthening surveillance, and infection control (Mendelson and Matsoso, 2014, 2015; Shallcross and Davies, 2014; Shallcross et al, 2015). India too has enormous distress due to multidrug-resistant infections; to enhance the epidemiological monitoring and evaluate the extent of AMR burden, the Indian Government initiated the research and surveillance program [Indian Council of Medical Research—Antimicrobial Resistance Surveillance and Research Network (ICMR-AMRSN)] in 2013 (Laxminarayan et al, 2013; Kaur et al, 2019; Veeraraghavan and Walia, 2019). The WHO Indian office and Department of Biotechnology published the first Indian pathogen priority list recently to guide future novel antimicrobial interventions against major clinically significant bacteria

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