Vibrio cholerae O1 associated with recent endemic cholera shows temporal changes in serotype, genotype, and drug-resistance patterns in Bangladesh

Abstract

Background Despite the advancement in our understanding of cholera and its etiological agent, V. cholerae, the prevention and treatment of the disease are often hindered due to rapid changes in drug response pattern, serotype, and the major genomic islands namely, the cholera toxin phage, and related genetic characteristics. In the present study, V. cholerae (n = 172) associated with endemic cholera in Dhaka during the years 2015–2021 were analyzed for major phenotypic and genetic characteristics, including drug resistance patterns. Results Results revealed that the V. cholerae strains belonged to serogroup O1 biotype El Tor carrying El Tor -specific genes rtxC, tcpA El Tor, and hlyA El Tor, but possessed classical-biotype cholera toxin. Serotypes of V. cholerae strains differed temporally in predominance with Inaba during 2015–2017, and again in 2020–2021, while Ogawa was the predominant serotype in 2018–2019. Also, ctxB1 was predominant in V. cholerae associated with cholera during 2015–2017, while ctxB7 was predominant in 2018, and in the subsequent years, as observed until 2021. V. cholerae strains differed in their antibiotic resistance pattern with a majority (97%) being multi-drug resistant (MDR) and belonging to eight sub-groups. Notably, one of these MDR strains was resistant to eleven of the eighteen antibiotics tested, with resistance to fourth-generation cephalosporin (cefepime), and aztreonam. This extreme drug resistant (XDR) strain carried resistance-related genes namely, extended-spectrum β-lactamases (ESBL), blaOXA-1 and blaPER-3. Conclusion The observed temporal switching of serotypes, as well as the ctxB genotype, and the emergence of MDR/XDR V. cholerae and their association with endemic cholera in Dhaka underscore the need for routine monitoring of the pathogen for proper patient management.

Signature genomic traits of the core and accessory genome of Vibrio Cholerae O1 drive lineage transmission and disease severity

“…1. Consistent with previous studies 9,14 , a serotype switch was observed, with Inaba predominantly present in 2016 and 2017, followed by a predominance of Ogawa samples in 2018 and 2019 (Fig. S1).…”

Genomic attributes of Vibrio cholerae O1 responsible for 2022 massive cholera outbreak in Bangladesh

“…While most of the global clade strains are known to possess seven AMR genes, T13 strains harbored only three, similarly observed for 30% of related Indian strains, hence some evidence for concluding the relatively drug-sensitive T13 strains transmitted from India to Africa as the T13 strains. A BD-2 strain carrying 14 AMR genes (aac(6')lb-cr5, aph(3")-lb, aph(6)-ld, blaOXA-1, blaPER-3, catB3, catB9, dfrA1, dfrA15, mph(A), sul1, sul2, tetA(D), and varG) and showing resistance to all of the eleven tested drugs (Cephalothin (KF), Streptomycin (S), Cefixime (CFM), Ceftriaxone (CRO), Nalidixic Acid (NA), Sulfamethoxazole/Trimethoprim (SXT), Cefepime (FEP), Mecillinam (MEL), Ciprofloxacin (CIP), Ampicillin (AMP), Aztreonam (ATM)) 27 may be considered a remnant of the lineage during transition while BD-1.2 was predominant, with perhaps extreme drug resistance the result of intense selective pressure as the two lineages fights to establish their respective niches 32 . The recent observation of the switch in serotype from Ogawa to Inaba of BD-1.2, coexistence of both serotypes, and subsequent massive cholera outbreak in Bangladesh is remarkable, since cholera outbreaks have been linked with serotype switching 33 .…”

“…We tested additional V. cholerae by randomly selecting 30 strains isolated between March and September 2022 in order to support our study findings and strengthen the conclusions made. The ctxB genotype was determined by a doublemismatch-amplification mutation assay (DMAMA) PCR and drug response patterns using disk diffusion assays 27 . According to our results, all of the tested strains carried ctxB7, and proved tetracycline sensitive as observed for the BD-1.2 (Supplementary Table 6).…”

“…The 21 outbreak strains subjected to whole genome sequencing in the present study were compared with 960 El Tor strains of the ongoing 7th cholera pandemic isolated between 1957 and 2021 from 88 countries. Additional 30 El Tor strains isolated from cholera patients admitted at icddr,b hospital (March-September, 2022) were tested for serotype, ctxB genotype, and drug resistance patterns 27 to increase the power of the study. This study did not need participant consent since there was no risk involved, no personally identifiable information or identifiable biospecimens were collected, and no follow-up was made after collecting the stool samples.…”