Cargando…

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

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 seve...

Descripción completa

Detalles Bibliográficos
Autores principales: Bengtsson, Rebecca J., Simpkin, Adam J., Pulford, Caisey V., Low, Ross, Rasko, David A., Rigden, Daniel J., Hall, Neil, Barry, Eileen M., Tennant, Sharon M., Baker, Kate S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8813619/
https://www.ncbi.nlm.nih.gov/pubmed/35102306
http://dx.doi.org/10.1038/s41564-021-01054-z
_version_ 1784644898694103040
author Bengtsson, Rebecca J.
Simpkin, Adam J.
Pulford, Caisey V.
Low, Ross
Rasko, David A.
Rigden, Daniel J.
Hall, Neil
Barry, Eileen M.
Tennant, Sharon M.
Baker, Kate S.
author_facet Bengtsson, Rebecca J.
Simpkin, Adam J.
Pulford, Caisey V.
Low, Ross
Rasko, David A.
Rigden, Daniel J.
Hall, Neil
Barry, Eileen M.
Tennant, Sharon M.
Baker, Kate S.
author_sort Bengtsson, Rebecca J.
collection PubMed
description 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.
format Online
Article
Text
id pubmed-8813619
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-88136192022-02-09 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 Barry, Eileen M. Tennant, Sharon M. Baker, Kate S. Nat Microbiol Article 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. Nature Publishing Group UK 2022-01-31 2022 /pmc/articles/PMC8813619/ /pubmed/35102306 http://dx.doi.org/10.1038/s41564-021-01054-z Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Bengtsson, Rebecca J.
Simpkin, Adam J.
Pulford, Caisey V.
Low, Ross
Rasko, David A.
Rigden, Daniel J.
Hall, Neil
Barry, Eileen M.
Tennant, Sharon M.
Baker, Kate S.
Pathogenomic analyses of Shigella isolates inform factors limiting shigellosis prevention and control across LMICs
title Pathogenomic analyses of Shigella isolates inform factors limiting shigellosis prevention and control across LMICs
title_full Pathogenomic analyses of Shigella isolates inform factors limiting shigellosis prevention and control across LMICs
title_fullStr Pathogenomic analyses of Shigella isolates inform factors limiting shigellosis prevention and control across LMICs
title_full_unstemmed Pathogenomic analyses of Shigella isolates inform factors limiting shigellosis prevention and control across LMICs
title_short Pathogenomic analyses of Shigella isolates inform factors limiting shigellosis prevention and control across LMICs
title_sort pathogenomic analyses of shigella isolates inform factors limiting shigellosis prevention and control across lmics
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8813619/
https://www.ncbi.nlm.nih.gov/pubmed/35102306
http://dx.doi.org/10.1038/s41564-021-01054-z
work_keys_str_mv AT bengtssonrebeccaj pathogenomicanalysesofshigellaisolatesinformfactorslimitingshigellosispreventionandcontrolacrosslmics
AT simpkinadamj pathogenomicanalysesofshigellaisolatesinformfactorslimitingshigellosispreventionandcontrolacrosslmics
AT pulfordcaiseyv pathogenomicanalysesofshigellaisolatesinformfactorslimitingshigellosispreventionandcontrolacrosslmics
AT lowross pathogenomicanalysesofshigellaisolatesinformfactorslimitingshigellosispreventionandcontrolacrosslmics
AT raskodavida pathogenomicanalysesofshigellaisolatesinformfactorslimitingshigellosispreventionandcontrolacrosslmics
AT rigdendanielj pathogenomicanalysesofshigellaisolatesinformfactorslimitingshigellosispreventionandcontrolacrosslmics
AT hallneil pathogenomicanalysesofshigellaisolatesinformfactorslimitingshigellosispreventionandcontrolacrosslmics
AT barryeileenm pathogenomicanalysesofshigellaisolatesinformfactorslimitingshigellosispreventionandcontrolacrosslmics
AT tennantsharonm pathogenomicanalysesofshigellaisolatesinformfactorslimitingshigellosispreventionandcontrolacrosslmics
AT bakerkates pathogenomicanalysesofshigellaisolatesinformfactorslimitingshigellosispreventionandcontrolacrosslmics