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 ORCID: 0000-0002-7565-8937, Hall, Neil, Barry, Eileen M, Tennant, Sharon M and Baker, Kate S ORCID: 0000-0001-5850-1949 (2022) Pathogenomic analyses of Shigella isolates inform factors limiting shigellosis prevention and control across LMICs. NATURE MICROBIOLOGY, 7 (2). 251-+.

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Official URL: http://dx.doi.org/10.1038/s41564-021-01054-z

Abstract

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
Uncontrolled Keywords:	Humans, Shigella, Shigella sonnei, Dysentery, Bacillary, Ciprofloxacin, Evolution, Molecular, Drug Resistance, Bacterial, Genome, Bacterial, Developing Countries, Child, Child, Preschool, Global Health, Whole Genome Sequencing
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User:	Symplectic Admin
Date Deposited:	09 Feb 2022 10:34
Last Modified:	18 Jan 2023 21:13
DOI:	10.1038/s41564-021-01054-z
Open Access URL:	https://www.nature.com/articles/s41564-021-01054-z
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3148585