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YfiB: An Outer Membrane Protein Involved in the Virulence of Shigella flexneri
The intracellular pathogen Shigella flexneri, which is the causative agent of bacillary dysentery, significantly influences the worldwide implication of diarrheal infections, consequentially causing about 1.1 million deaths each year. Due to a nonavailability of an authorized vaccine and the upsurge...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8948675/ https://www.ncbi.nlm.nih.gov/pubmed/35336228 http://dx.doi.org/10.3390/microorganisms10030653 |
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author | Sen, Tanuka Verma, Naresh K. |
author_facet | Sen, Tanuka Verma, Naresh K. |
author_sort | Sen, Tanuka |
collection | PubMed |
description | The intracellular pathogen Shigella flexneri, which is the causative agent of bacillary dysentery, significantly influences the worldwide implication of diarrheal infections, consequentially causing about 1.1 million deaths each year. Due to a nonavailability of an authorized vaccine and the upsurge of multidrug resistance amongst Shigella strains, there has been a huge demand for further genetic analyses which could help in the advancement of new/improved drugs, and finding vaccine candidates against the pathogen. The present study aims to illustrate the role of the yfiB gene in Shigella virulence, part of the periplasmic YfiBNR tripartite signalling system. This system is involved in the regulation of cyclic-di-GMP levels inside the bacterial cells, a vital messenger molecule impacting varied cellular processes such as biofilm formation, cytotoxicity, motility, synthesis of exopolysaccharide, and other virulence mechanisms such as adhesion and invasion of the bacteria. Through a combination of genetic, biochemical, and virulence assays, we show how knocking out the yfiB gene can disrupt the entire YfiBNR system and affect the native c-di-GMP levels. We found that this subsequently causes a negative effect on the biofilm formation, bacterial invasion, host–surface attachment, and the overall virulence of Shigella. This study also carried out a structural and functional assessment of the YfiB protein and determined critical amino acid residues, essential for proper functioning of this signalling system. The present work improves our understanding of the in vivo persistence and survival of Shigella, brings light to the c-di-GMP led regulation of Shigella virulence, and provides a prospective new target to design anti-infection drugs and vaccines against S. flexneri and other bacterial pathogens. |
format | Online Article Text |
id | pubmed-8948675 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-89486752022-03-26 YfiB: An Outer Membrane Protein Involved in the Virulence of Shigella flexneri Sen, Tanuka Verma, Naresh K. Microorganisms Article The intracellular pathogen Shigella flexneri, which is the causative agent of bacillary dysentery, significantly influences the worldwide implication of diarrheal infections, consequentially causing about 1.1 million deaths each year. Due to a nonavailability of an authorized vaccine and the upsurge of multidrug resistance amongst Shigella strains, there has been a huge demand for further genetic analyses which could help in the advancement of new/improved drugs, and finding vaccine candidates against the pathogen. The present study aims to illustrate the role of the yfiB gene in Shigella virulence, part of the periplasmic YfiBNR tripartite signalling system. This system is involved in the regulation of cyclic-di-GMP levels inside the bacterial cells, a vital messenger molecule impacting varied cellular processes such as biofilm formation, cytotoxicity, motility, synthesis of exopolysaccharide, and other virulence mechanisms such as adhesion and invasion of the bacteria. Through a combination of genetic, biochemical, and virulence assays, we show how knocking out the yfiB gene can disrupt the entire YfiBNR system and affect the native c-di-GMP levels. We found that this subsequently causes a negative effect on the biofilm formation, bacterial invasion, host–surface attachment, and the overall virulence of Shigella. This study also carried out a structural and functional assessment of the YfiB protein and determined critical amino acid residues, essential for proper functioning of this signalling system. The present work improves our understanding of the in vivo persistence and survival of Shigella, brings light to the c-di-GMP led regulation of Shigella virulence, and provides a prospective new target to design anti-infection drugs and vaccines against S. flexneri and other bacterial pathogens. MDPI 2022-03-18 /pmc/articles/PMC8948675/ /pubmed/35336228 http://dx.doi.org/10.3390/microorganisms10030653 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Sen, Tanuka Verma, Naresh K. YfiB: An Outer Membrane Protein Involved in the Virulence of Shigella flexneri |
title | YfiB: An Outer Membrane Protein Involved in the Virulence of Shigella flexneri |
title_full | YfiB: An Outer Membrane Protein Involved in the Virulence of Shigella flexneri |
title_fullStr | YfiB: An Outer Membrane Protein Involved in the Virulence of Shigella flexneri |
title_full_unstemmed | YfiB: An Outer Membrane Protein Involved in the Virulence of Shigella flexneri |
title_short | YfiB: An Outer Membrane Protein Involved in the Virulence of Shigella flexneri |
title_sort | yfib: an outer membrane protein involved in the virulence of shigella flexneri |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8948675/ https://www.ncbi.nlm.nih.gov/pubmed/35336228 http://dx.doi.org/10.3390/microorganisms10030653 |
work_keys_str_mv | AT sentanuka yfibanoutermembraneproteininvolvedinthevirulenceofshigellaflexneri AT vermanareshk yfibanoutermembraneproteininvolvedinthevirulenceofshigellaflexneri |