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 (ΔwcaM ΔcsgA 
ΔyihO ΔbcsE) 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 ΔwcaM ΔcsgA ΔyihO ΔbcsE mutant 
strain. While the ΔwcaM ΔcsgA ΔyihO ΔbcsE 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.