Salmonella promotes 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 enterica serovar 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 the mgtC gene exhibited increased cellulose levels due to increased expression of the cellulose synthase gene bcsA and of cyclic diguanylate, the allosteric activator of the BcsA protein. Inactivation of bcsA restored wild-type virulence to the Salmonella mgtC mutant, 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 tradeoff between acute virulence and transmission.biofilm | magnesium | ATP

Adherent-Invasive Escherichia coli Production of Cellulose Influences Iron-Induced Bacterial Aggregation, Phagocytosis, and Induction of Colitis

“…The contribution of cellulose to the in vivo fitness and virulence potential of E. coli and related bacteria has been investigated only in UPEC strains in the urinary tract (35,77) and S. Typhimurium when administered intraperitoneally (78). Therefore, to establish whether cellulose contributes to the colitogenicity of AIEC in the GI tract, the severity of colitis was assessed in Il10 Ϫ/Ϫ mice monoassociated with NC101 or the cellulose-deficient bcsA mutant.…”

When Too Much ATP Is Bad for Protein Synthesis

“…However, in the central nervous system, binding of extracellular ATP to purinergic receptors triggers an inflammatory response that leads to homeostatic regulation in small doses but to neuron dysfunction and death in large doses [2,3]. And in the bacterial pathogen Salmonella enterica serovar Typhimurium, high levels of intracellular ATP can result in decreased virulence and growth arrest in media containing low magnesium (Mg 2+ ) [4-6]. Because ATP has a high affinity for Mg 2+ [7] (Table 1), a non-physiological increase in ATP levels can deplete free cytosolic Mg 2+ pools, and thus, disrupt essential Mg 2+ -dependent cellular processes including protein synthesis [8,9].…”

Regulation and function of the Salmonella MgtC virulence protein

“…This is because the mgtC mutant adheres together at the surface of a glass tube, constituting biofilms. The nature of exopolysaccharides holding the mutant cells together turned out to be cellulose (Pontes et al, 2015). The mgtC mutant accumulates ATP levels and subsequently increases c-di-GMP levels, which activate the bcsA gene encoding a cellulose synthase (Pontes et al, 2015).…”

“…The nature of exopolysaccharides holding the mutant cells together turned out to be cellulose (Pontes et al, 2015). The mgtC mutant accumulates ATP levels and subsequently increases c-di-GMP levels, which activate the bcsA gene encoding a cellulose synthase (Pontes et al, 2015). This means that Salmonella represses cellulose production during infection by expressing MgtC proteins.…”

“…This means that Salmonella represses cellulose production during infection by expressing MgtC proteins. Interestingly, the bcsA mutant has a hypervirulent phenotype in a mouse infection model, indicating that cellulose acts as an antivirulence factor during Salmonella infection (Pontes et al, 2015).…”