RgpF Is Required for Maintenance of Stress Tolerance and Virulence in Streptococcus mutans.

Bacterial cell wall dynamics have been implicated as important determinants of cellular physiology, stress tolerance, and virulence. In , the cell wall is composed primarily of a rhamnose-glucose polysaccharide (RGP) linked to the peptidoglycan. Despite extensive studies describing its formation and composition, the potential roles for RGP in biology have not been well investigated. The present study characterizes the impact of RGP disruption as a result of the deletion of , the gene encoding a rhamnosyltransferase involved in the construction of the core polyrhamnose backbone of RGP. The Δ mutant strain displayed an overall reduced fitness compared to the wild type, with heightened sensitivities to various stress-inducing culture conditions and an inability to tolerate acid challenge. The loss of caused a perturbation of membrane-associated functions known to be critical for aciduricity, a hallmark of acid tolerance. The proton gradient across the membrane was disrupted, and the Δ mutant strain was unable to induce activity of the FF ATPase in cultures grown under low-pH conditions. Further, the virulence potential of was also drastically reduced following the deletion of The Δ mutant strain produced significantly less robust biofilms, indicating an impairment in its ability to adhere to hydroxyapatite surfaces. Additionally, the Δ mutant lost competitive fitness against oral peroxigenic streptococci, and it displayed significantly attenuated virulence in an infection model. Collectively, these results highlight a critical function of the RGP in the maintenance of overall stress tolerance and virulence traits in The cell wall of , the bacterium most commonly associated with tooth decay, is abundant in rhamnose-glucose polysaccharides (RGP). While these structures are antigenically distinct to , the process by which they are formed and the enzymes leading to their construction are well conserved among streptococci. The present study describes the consequences of the loss of RgpF, a rhamnosyltransferase involved in RGP construction. The deletion of resulted in severe ablation of the organism's overall fitness, culminating in significantly attenuated virulence. Our data demonstrate an important link between the RGP and cell wall physiology of , affecting critical features used by the organism to cause disease and providing a potential novel target for inhibiting the pathogenesis of .