@article{937c717b808b4ea088770501b73eda2e,
title = "Quantitative proteomics uncovers the interaction between a virulence factor and mutanobactin synthetases in Streptococcus mutans",
abstract = "Streptococcus mutans, 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 S. mutans by altering the biofilm matrix composition and cariogenicity. In this study, we further characterized the smu_833 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 H2O2 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 S. mutans 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 smu_833 mutant, the deletion of the mutanobactin gene cluster rendered the mutant less competitive against H2O2-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.",
keywords = "Competition, Mutacin, Mutanobactin, Oxidative stress, Proteomics, Streptococcus mutans",
author = "Katherine Rainey and Landon Wilson and Stephen Barnes and Hui Wu",
note = "Funding Information: This study was supported by the National Institute of Dental Craniofacial Research Institute of National Institutes of Health grants F31DE025805 (K.R.), R01DE022350 (H.W.), and R01DE017954 (H.W.). The mass spectrometer was purchased through a NIH Shared Instrumentation Grant (S10 RR027822 to S.B.). Funds for the operation of the Targeted Metabolomics and Proteomics Laboratory come in part from the UAB O{\textquoteright}Brien Acute Kidney Injury Center (P30 DK079337). Funding Information: This study was supported by the National Institute of Dental Craniofacial Research Institute of National Institutes of Health grants F31DE025805 (K.R.), R01DE022350 (H.W.), and R01DE017954 (H.W.). The mass spectrometer was purchased through a NIH Shared Instrumentation Grant (S10 RR027822 to S.B.). Funds for the operation of the Targeted Metabolomics and Proteomics Laboratory come in part from the UAB O'Brien Acute Kidney Injury Center (P30 DK079337). We thank Fengxia Qi at the University of Oklahoma Health Science Center for the mutanobactin (mub) deletion mutant strain. K.R. and H.W. designed experiments and wrote the manuscript. L.W. and S.B. conducted the quantitative SWATH proteomics and data analysis. K.R. conducted the remaining experimetns. All authors reviewed the final draft of the manuscript. Publisher Copyright: {\textcopyright} 2019 Rainey et al. Copyright: Copyright 2019 Elsevier B.V., All rights reserved.",
year = "2019",
doi = "10.1128/mSphere.00429-19",
language = "English (US)",
volume = "4",
journal = "mSphere",
issn = "2379-5042",
publisher = "American Society for Microbiology",
number = "5",
}