Salmonella enterica serovar Typhi in Bangladesh: exploration of genomic diversity and antimicrobial resistance

Tanmoy, A. M., Westeel, E., De Bruyne, K., Goris, J., Rajoharison, A., Sajib, M. S. I. , van Belkum, A., Saha, S. K., Komurian-Pradel, F. and Endtz, H. P. (2018) Salmonella enterica serovar Typhi in Bangladesh: exploration of genomic diversity and antimicrobial resistance. mBio, 9(6), e02112-18. (doi: 10.1128/mbio.02112-18) (PMID:30425150) (PMCID:PMC6234861)

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Abstract

Typhoid fever, caused by Salmonella enterica serovar Typhi, is a global public health concern due to increasing antimicrobial resistance (AMR). Characterization of S. Typhi genomes for AMR and the evolution of different lineages, especially in countries where typhoid fever is endemic such as Bangladesh, will help public health professionals to better design and implement appropriate preventive measures. We studied whole-genome sequences (WGS) of 536 S. Typhi isolates collected in Bangladesh during 1999 to 2013 and compared those sequences with data from a recent outbreak in Pakistan reported previously by E. J. Klemm, S. Shakoor, A. J. Page, F. N. Qamar, et al. (mBio 9:e00105-18, 2018, https://doi.org/10.1128/mBio.00105-18), and a laboratory surveillance in Nepal reported previously by C. D. Britto, Z. A. Dyson, S. Duchene, M. J. Carter, et al. [PLoS Negl. Trop. Dis. 12(4):e0006408, 2018, https://doi.org/10.1371/journal.pntd.0006408]. WGS had high sensitivity and specificity for prediction of ampicillin, chloramphenicol, co-trimoxazole, and ceftriaxone AMR phenotypes but needs further improvement for prediction of ciprofloxacin resistance. We detected a new local lineage of genotype 4.3.1 (named lineage Bd) which recently diverged into a sublineage (named Bdq) containing qnr genes associated with high-level ciprofloxacin resistance. We found a ceftriaxone-resistant isolate with the blaCTX-M-15 gene and a genotype distinct from the genotypes of extensively drug-resistant (XDR) isolates from Pakistan. This result suggests a different source and geographical origin of AMR. Genotype 4.3.1 was dominant in all three countries but formed country-specific clusters in the maximum likelihood phylogenetic tree. Thus, multiple independent genetic events leading to ciprofloxacin and ceftriaxone resistance took place in these neighboring regions of Pakistan, Nepal, and Bangladesh. These independent mutational events may enhance the risk of global spread of these highly resistant clones. A short-term global intervention plan is urgently needed. IMPORTANCE: Typhoid fever, caused by Salmonella enterica serovar Typhi, is responsible for an estimated burden of approximately 17 million new episodes per year worldwide. Adequate and timely antimicrobial treatment invariably cures typhoid fever. The increasing antimicrobial resistance (AMR) of S. Typhi severely limits the treatment options. We studied whole-genome sequences (WGS) of 536 S. Typhi isolates collected in Bangladesh between 1999 and 2013 and compared those sequences with data from a recent outbreak in Pakistan and a laboratory surveillance in Nepal. The analysis suggests that multiple ancestral origins of resistance against ciprofloxacin and ceftriaxone are present in three countries. Such independent genetic events and subsequent dissemination could enhance the risk of a rapid global spread of these highly resistant clones. Given the current treatment challenges, vaccination seems to be the most appropriate short-term intervention to reduce the disease burden of typhoid fever at a time of increasing AMR.

Item Type:Articles
Additional Information:This study received funding from the EU Horizon 2020 research and innovation program under grant agreement no. 643476.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Sajib, Mohammad Saiful Islam
Authors: Tanmoy, A. M., Westeel, E., De Bruyne, K., Goris, J., Rajoharison, A., Sajib, M. S. I., van Belkum, A., Saha, S. K., Komurian-Pradel, F., and Endtz, H. P.
College/School:College of Medical Veterinary and Life Sciences
Journal Name:mBio
Publisher:American Society for Microbiology
ISSN:2161-2129
ISSN (Online):2150-7511
Published Online:13 November 2018
Copyright Holders:Copyright © 2018 Tanmoy et al.
First Published:First published in mBio 9(6):e02112-18
Publisher Policy:Reproduced under a Creative Commons Licence

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