Quantitative Proteomics Uncovers the Interaction Between a Virulence Factor and Mutanobactin Synthetases in

, the primary etiological agent of tooth decay, has developed multiple adhesion and virulence factors which enable it to colonize and compete with other bacteria. The putative glycosyltransferase SMU_833 is important for the virulence of by altering the biofilm matrix composition and cariogenicity. In this study, we further characterized the mutant by evaluating its effects on bacterial fitness. Loss of SMU_833 led to extracellular DNA-dependent bacterial aggregation. In addition, the mutant was more susceptible to oxidative stress and less competitive against HO producing oral streptococci. Quantitative proteomics analysis revealed that SMU_833 deficiency resulted in the significant downregulation of 10 proteins encoded by a biosynthetic gene cluster responsible for the production of mutanobactin, a compound produced by which helps it survive oxidative stress. Tandem affinity purification demonstrated that SMU_833 interacts with the synthetic enzymes responsible for the production of mutanobactin. Similar to the mutant, the deletion of the mutanobactin gene cluster rendered the mutant less competitive against HO-producing streptococci. Our studies revealed a new link between SMU_833 virulence and mutanobactin, suggesting that SMU_833 represents a new virulent target that can be used to develop potential anticaries therapeutics. is the major bacterium associated with dental caries. In order to thrive on the highly populated tooth surface and cause disease, must be able to protect itself from hydrogen peroxide-producing commensal bacteria and compete effectively against the neighboring microbes. produces mutacins, small antimicrobial peptides which help control the population of competing bacterial species. In addition, produces a peptide called mutanobactin, which offers protection against oxidative stress. Here, we uncover a new link between the putative glycosyltransferase SMU_833 and the mutanobactin-synthesizing protein complex through quantitative proteomic analysis and a tandem-affinity protein purification scheme. Furthermore, we show that SMU_833 mediates bacterial sensitivity to oxidative stress and bacterial ability to compete with commensal streptococci. This study has revealed a previously unknown association between SMU_833 and mutanobactin and demonstrated the importance of SMU_833 in the fitness of .