Salmonella extracellular matrix components influence biofilm formation and gallbladder colonization

AUTHORS

Adcox, HE.; Vasicek, EM.; Dwivedi, V.; Hoang, KV.; Turner, J.; and Gunn, JS.

ABSTRACT

Salmonella enterica serovar Typhi, the causative agent of typhoid fever in humans, form 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 S. Typhimurium, the murine model of S Typhi, in which various ECM genes were deleted or added were created to examine biofilm formation and colonization and persistence in the gallbladder. Studies show that curli contributes most significantly to biofilm formation. Expressing Vi-antigen decreased biofilm formation in vitro and virulence and bacterial survival in vivo without altering examined gallbladder pro- or anti-inflammatory cytokines. Oppositely, loss of all ECM components (ΔwcaMΔcsgAΔyihOΔbcsE) increased virulence and bacterial survival in vivo and reduced gallbladder 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 ΔwcaMΔcsgAΔyihOΔbcsE strain. While the ΔwcaMΔcsgAΔyihOΔbcsE mutant was not altered in resistance to complement or growth in macrophages, it attached and invaded macrophages better than the WT strain. These data suggest that ECM components have varying 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.

Click here to view the article, published in Infection and Immunity.