RESISTOME PROFILES AND GENOME DYNAMICS OF MULTI-DRUG RESISTANT SHIGELLA SPP. ISOLATED IN BANGLADESH

Abstract

Intro: Multi-drug resistance (MDR) in Shigella remains public health burden, especially in resource-limited settings like Bangladesh. However, genome-wide studies to track the origination and epidemiology of antimicrobial resistant (AMR) genes are scarce here. Therefore, the study was designed to assess outraging drug resistance in Shigella and to map AMR genes in the genome. Methods: Shigella strains were isolated from stool specimens of diarrheal patients in Bangladesh. MDR phenomena were determined by antimicrobial susceptibility tests (AST). Whole-genome sequencing (WGS) was performed on the Illumina platform and the genomes were analyzed using many bioinformatics approaches. Findings: We screened 11 MDR and 2 non-MDR Shigella strains from the AST results and subjected them to WGS analysis. Analyzing the genomes, we identified 27 AMR genes of 9 different classes arrayed as pathogenicity islands in mobile genetic elements (MGEs). The extended-spectrum beta-lactamase (ESBL) gene blaCTX-M-15 was present in 4 MDR strains as IS1380-blaCTX-M-15-WbuC gene cassette in Tn7 transposon. The blaCTX-M-15 gene was not novel but the island was very new in Shigella. Another plasmid-mediated ESBL-gene blaTEM-1 was neighboring the ermB-IS26-mph(A)-mrx-mph(R)(A)-IS6100 macrolideresistant gene cluster. The aminoglycoside-resistant gene aadA1 was found in the Tn7 transposon of 6 MDR strains arrayed with dfrA gene, integrases (int1 and int2), and different transposes. Macrolide resistance genes were identified in two separate plasmid-borne gene cassettes like ermB-IS26-mph(A)-mrx-mph(R)(A)-IS6100 and unique mph(E)-msr(E)-IS482-IS6 in 3 and 2 MDR Shigella strains respectively. The incidence rate of the highly pathogenic ermB-IS26-mph(A)-mrxmph (R)(A)-IS6100-blaTEM-1 containing plasmid was found to be exponentially increasing globally. Type-1 CRISPRs were identified in 85% of the strains where most of the spacers were incorporated from the Escherichia coli H240 plasmid. Conclusion: Drug-resistant gene clusters evolve and propagate among enteropathogens through MGEs. The rise of stronger Shigella superbug can be predicted from the study, however, global epidemiological tracking of MDR related MGEs in Shigella is needed to unveil the AMR-network.