Pathogenomic analyses of Shigella isolates inform factors limiting shigellosis prevention and control across LMICs

Bengtsson, Rebecca J., Simpkin, Adam J., Pulford, Caisey V., Low, Ross, Rasko, David A., Rigden, Daniel J., Hall, Neil ORCID:, Barry, Eileen M., Tennant, Sharon M. and Baker, Kate S. (2022) Pathogenomic analyses of Shigella isolates inform factors limiting shigellosis prevention and control across LMICs. Nature Microbiology, 7 (2). pp. 251-261. ISSN 2058-5276

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Shigella spp. are the leading bacterial cause of severe childhood diarrhoea in low- and middle-income countries (LMICs), are increasingly antimicrobial resistant and have no widely available licenced vaccine. We performed genomic analyses of 1,246 systematically collected shigellae sampled from seven countries in sub-Saharan Africa and South Asia as part of the Global Enteric Multicenter Study (GEMS) between 2007 and 2011, to inform control and identify factors that could limit the effectiveness of current approaches. Through contemporaneous comparison among major subgroups, we found that S. sonnei contributes ≥6-fold more disease than other Shigella species relative to its genomic diversity, and highlight existing diversity and adaptative capacity among S. flexneri that may generate vaccine escape variants in <6 months. Furthermore, we show convergent evolution of resistance against ciprofloxacin, the current WHO-recommended antimicrobial for the treatment of shigellosis, among Shigella isolates. This demonstrates the urgent need to integrate existing genomic diversity into vaccine and treatment plans for Shigella, providing a framework for the focused application of comparative genomics to guide vaccine development, and the optimization of control and prevention strategies for other pathogens relevant to public health policy considerations.

Item Type: Article
Additional Information: Funding Information: We thank the members of Baker group and Lab H at the University of Liverpool, and R. Bacigalupe at KU Leuven for invaluable discussions; J. Hinton and B. P. Sepulveda for orchestrating the thermolysate shipping; S. Haldenby, M. Gemmell, R. Gregory and the Centre for Genomics Research, University of Liverpool for technical support; Dr I. Kasumba, J. Jones, S. Sen and J.-P.-Booth for preparing GEMS Shigella isolates for sequencing and antimicrobial testing. This work was supported by a UKRI MRC NIRG award (MR/R020787/1, KSB), the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services (U19AI110820, DR), and by both a Global Challenges Research Fund (GCRF) data and resources grant (BBS/OS/GC/000009D, NH) and the BBSRC Core Capability Grant to the Earlham Institute (BB/CCG1720/1, NH). Next-generation sequencing and library construction were delivered via the BBSRC National Capability in Genomics and Single Cell (BB/CCG1720/1, NH) at Earlham Institute, by members of the Genomics Pipelines Group. K.S.B. was supported by a Wellcome Trust Clinical Research Career Development Award (106690/A/14/Z) and an Academy of Medical Sciences Springboard award (SBF002/1114), and is affiliated with the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Gastrointestinal Infections at the University of Liverpool in partnership with Public Health England (PHE) and in collaboration with the University of Warwick. The views expressed herein are those of the author(s) and do not necessarily represent those of the NHS, the NIHR, the Department of Health and Social Care or Public Health England.
Uncontrolled Keywords: applied microbiology and biotechnology,microbiology (medical),genetics,cell biology,microbiology,immunology,sdg 3 - good health and well-being ,/dk/atira/pure/subjectarea/asjc/2400/2402
Faculty \ School: Faculty of Science > School of Biological Sciences
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Depositing User: LivePure Connector
Date Deposited: 17 Feb 2022 14:30
Last Modified: 22 Oct 2022 17:35
DOI: 10.1038/s41564-021-01054-z


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