Dataset Information

Salmonella Extracellular Matrix Components Influence Biofilm Formation and Gallbladder Colonization.

ABSTRACT: Salmonella enterica serovar Typhi, the causative agent of typhoid fever in humans, forms biofilms encapsulated by an extracellular matrix (ECM). Biofilms facilitate colonization and persistent infection in gallbladders of humans and mouse models of chronic carriage. Individual roles of matrix components have not been completely elucidated in vitro or in vivo To examine individual functions, strains of Salmonella enterica serovar Typhimurium, the murine model of S Typhi, in which various ECM genes were deleted or added, were created to examine biofilm formation, colonization, and persistence in the gallbladder. Studies show that curli contributes most significantly to biofilm formation. Expression of Vi antigen decreased biofilm formation in vitro and virulence and bacterial survival in vivo without altering the examined gallbladder pro- or anti-inflammatory cytokines. Oppositely, loss of all ECM components (?wcaM ?csgA ?yihO ?bcsE) increased virulence and bacterial survival in vivo and reduced gallbladder interleukin-10 (IL-10) levels. Colanic acid and curli mutants had the largest defects in biofilm-forming ability and contributed most significantly to the virulence increase of the ?wcaM ?csgA ?yihO ?bcsE mutant strain. While the ?wcaM ?csgA ?yihO ?bcsE mutant was not altered in resistance to complement or growth in macrophages, it attached and invaded macrophages better than the wild-type (WT) strain. These data suggest that ECM components have various levels of importance in biofilm formation and gallbladder colonization and that the ECM diminishes disseminated disease in our model, perhaps by reducing cell attachment/invasion and dampening inflammation by maintaining/inducing IL-10 production. Understanding how ECM components aid acute disease and persistence could lead to improvements in therapeutic treatment of typhoid fever patients.

SUBMITTER: Adcox HE

PROVIDER: S-EPMC5067756 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Salmonella Extracellular Matrix Components Influence Biofilm Formation and Gallbladder Colonization.

Adcox Haley E HE Vasicek Erin M EM Dwivedi Varun V Hoang Ky V KV Turner Joanne J Gunn John S JS

Infection and immunity 20161017 11

Salmonella enterica serovar Typhi, the causative agent of typhoid fever in humans, forms biofilms encapsulated by an extracellular matrix (ECM). Biofilms facilitate colonization and persistent infection in gallbladders of humans and mouse models of chronic carriage. Individual roles of matrix components have not been completely elucidated in vitro or in vivo To examine individual functions, strains of Salmonella enterica serovar Typhimurium, the murine model of S Typhi, in which various ECM gene ...[more]

PMID: 27600501

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Project description:Typhoid fever, a human-specific disease, is primarily caused by the pathogen Salmonella enterica serovar Typhi. It is estimated that 3 to 5% of people infected with typhoid fever become chronic carriers. Studies have demonstrated that a mechanism of chronic carriage involves biofilm formation on gallstone surfaces. In the course of a previous study using a chronic carriage mouse model, a Salmonella enterica serovar Typhimurium isolate was recovered from a mouse gallstone that exhibited a 2-fold increase in biofilm formation over the wild type. In order to identify the gene(s) responsible for the phenotype, the genomic sequences of this isolate and others were determined and compared. These sequences identified single nucleotide polymorphisms (SNPs) in 14 genes. Mutations in the most promising candidates, envZ and rcsB, were created, but neither showed increased biofilm-forming ability separately or in combination. The hyperbiofilm isolate did, however, present variations in cellular appendages observable using different techniques and a preferential binding to cholesterol. The isolate was also examined for systemic virulence and the ability to colonize the gallbladder/gallstones in a mouse model of chronic infection, demonstrating a systemic virulence defect and decreased gallbladder/gallstone colonization. Finally, to determine if the appearance of hyperbiofilm isolates could be replicated in vitro and if this was a common event, wild-type Salmonella spp. were grown long term in vitro under gallbladder-mimicking conditions, resulting in a high proportion of isolates that replicated the hyperbiofilm phenotype of the original isolate. Thus, Salmonella spp. acquire random mutations under the gallbladder/gallbladder-simulating conditions that may aid persistence but negatively affect systemic virulence.IMPORTANCE Chronic carriers are the main reservoirs for the spread of typhoid fever in regions of endemicity. Salmonella Typhi forms biofilms on gallstones in order to persist. A strain with enhanced biofilm-forming ability was recovered after a nine-month chronic-carriage mouse study. After sequencing this strain and recreating some of the mutations, we could not duplicate the phenotype. The isolate did show a difference in flagella, a preference to bind to cholesterol, and a systemic virulence defect. Finally, gallbladder conditions were simulated in vitro After 60?days, there was a 4.5-fold increase in hyperbiofilm isolates when a gallstone was present. These results indicate that Salmonella spp. can undergo genetic changes that improve persistence in gallbladder albeit at the cost of decreased virulence.

Dataset Information

Salmonella Extracellular Matrix Components Influence Biofilm Formation and Gallbladder Colonization.

Publications

Salmonella Extracellular Matrix Components Influence Biofilm Formation and Gallbladder Colonization.

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