Enhanced biofilm and extracellular matrix production by chronic carriage versus acute isolates of Salmonella Typhi.

Salmonella Typhi is the primary causative agent of typhoid fever; an acute systemic infection that leads to chronic carriage in 3-5% of individuals. Chronic carriers are asymptomatic, difficult to treat and serve as reservoirs for typhoid outbreaks. Understanding the factors that contribute to chron...

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Main Authors: Aishwarya Devaraj, Juan F González, Bradley Eichar, Gatan Thilliez, Robert A Kingsley, Stephen Baker, Marc W Allard, Lauren O Bakaletz, John S Gunn, Steven D Goodman
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2021-01-01
Series:PLoS Pathogens
Online Access:https://doi.org/10.1371/journal.ppat.1009209
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author Aishwarya Devaraj
Juan F González
Bradley Eichar
Gatan Thilliez
Robert A Kingsley
Stephen Baker
Marc W Allard
Lauren O Bakaletz
John S Gunn
Steven D Goodman
author_facet Aishwarya Devaraj
Juan F González
Bradley Eichar
Gatan Thilliez
Robert A Kingsley
Stephen Baker
Marc W Allard
Lauren O Bakaletz
John S Gunn
Steven D Goodman
author_sort Aishwarya Devaraj
collection DOAJ
description Salmonella Typhi is the primary causative agent of typhoid fever; an acute systemic infection that leads to chronic carriage in 3-5% of individuals. Chronic carriers are asymptomatic, difficult to treat and serve as reservoirs for typhoid outbreaks. Understanding the factors that contribute to chronic carriage is key to development of novel therapies to effectively resolve typhoid fever. Herein, although we observed no distinct clustering of chronic carriage isolates via phylogenetic analysis, we demonstrated that chronic isolates were phenotypically distinct from acute infection isolates. Chronic carriage isolates formed significantly thicker biofilms with greater biomass that correlated with significantly higher relative levels of extracellular DNA (eDNA) and DNABII proteins than biofilms formed by acute infection isolates. Importantly, extracellular DNABII proteins include integration host factor (IHF) and histone-like protein (HU) that are critical to the structural integrity of bacterial biofilms. In this study, we demonstrated that the biofilm formed by a chronic carriage isolate in vitro, was susceptible to disruption by a specific antibody against DNABII proteins, a successful first step in the development of a therapeutic to resolve chronic carriage.
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spelling doaj.art-6c0eb2f73ed747978ef1f2059f535e0c2022-12-21T19:16:59ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742021-01-01171e100920910.1371/journal.ppat.1009209Enhanced biofilm and extracellular matrix production by chronic carriage versus acute isolates of Salmonella Typhi.Aishwarya DevarajJuan F GonzálezBradley EicharGatan ThilliezRobert A KingsleyStephen BakerMarc W AllardLauren O BakaletzJohn S GunnSteven D GoodmanSalmonella Typhi is the primary causative agent of typhoid fever; an acute systemic infection that leads to chronic carriage in 3-5% of individuals. Chronic carriers are asymptomatic, difficult to treat and serve as reservoirs for typhoid outbreaks. Understanding the factors that contribute to chronic carriage is key to development of novel therapies to effectively resolve typhoid fever. Herein, although we observed no distinct clustering of chronic carriage isolates via phylogenetic analysis, we demonstrated that chronic isolates were phenotypically distinct from acute infection isolates. Chronic carriage isolates formed significantly thicker biofilms with greater biomass that correlated with significantly higher relative levels of extracellular DNA (eDNA) and DNABII proteins than biofilms formed by acute infection isolates. Importantly, extracellular DNABII proteins include integration host factor (IHF) and histone-like protein (HU) that are critical to the structural integrity of bacterial biofilms. In this study, we demonstrated that the biofilm formed by a chronic carriage isolate in vitro, was susceptible to disruption by a specific antibody against DNABII proteins, a successful first step in the development of a therapeutic to resolve chronic carriage.https://doi.org/10.1371/journal.ppat.1009209
spellingShingle Aishwarya Devaraj
Juan F González
Bradley Eichar
Gatan Thilliez
Robert A Kingsley
Stephen Baker
Marc W Allard
Lauren O Bakaletz
John S Gunn
Steven D Goodman
Enhanced biofilm and extracellular matrix production by chronic carriage versus acute isolates of Salmonella Typhi.
PLoS Pathogens
title Enhanced biofilm and extracellular matrix production by chronic carriage versus acute isolates of Salmonella Typhi.
title_full Enhanced biofilm and extracellular matrix production by chronic carriage versus acute isolates of Salmonella Typhi.
title_fullStr Enhanced biofilm and extracellular matrix production by chronic carriage versus acute isolates of Salmonella Typhi.
title_full_unstemmed Enhanced biofilm and extracellular matrix production by chronic carriage versus acute isolates of Salmonella Typhi.
title_short Enhanced biofilm and extracellular matrix production by chronic carriage versus acute isolates of Salmonella Typhi.
title_sort enhanced biofilm and extracellular matrix production by chronic carriage versus acute isolates of salmonella typhi
url https://doi.org/10.1371/journal.ppat.1009209
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