Salmonellapromotes virulence by repressing cellulose production

Abstract

Cellulose is the most abundant organic polymer on Earth. In bacteria, cellulose confers protection against environmental insults and is a constituent of biofilms typically formed on abiotic surfaces. We report that, surprisingly,Salmonella entericaserovar Typhimurium makes cellulose when inside macrophages. We determine that preventing cellulose synthesis increases virulence, whereas stimulation of cellulose synthesis inside macrophages decreases virulence. An attenuated mutant lacking themgtCgene exhibited increased cellulose levels due to increased expression of the cellulose synthase genebcsAand of cyclic diguanylate, the allosteric activator of the BcsA protein. Inactivation ofbcsArestored wild-type virulence to theSalmonella mgtCmutant, but not to other attenuated mutants displaying a wild-type phenotype regarding cellulose. Our findings indicate that a virulence determinant can promote pathogenicity by repressing a pathogen's antivirulence trait. Moreover, they suggest that controlling antivirulence traits increases long-term pathogen fitness by mediating a trade-off between acute virulence and transmission.