Quantitative Proteomics Uncovers the Interaction between a Virulence Factor and Mutanobactin Synthetases in <italic toggle="yes">Streptococcus mutans</italic>

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...

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Autores principales:	Katherine Rainey, Landon Wilson, Stephen Barnes, Hui Wu
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	Streptococcus mutans oxidative stress mutacin mutanobactin proteomics competition Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/dde0f3d3522949bab431a21cbcc21600
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spelling	oai:doaj.org-article:dde0f3d3522949bab431a21cbcc216002021-11-15T15:27:33ZQuantitative Proteomics Uncovers the Interaction between a Virulence Factor and Mutanobactin Synthetases in <italic toggle="yes">Streptococcus mutans</italic>10.1128/mSphere.00429-192379-5042https://doaj.org/article/dde0f3d3522949bab431a21cbcc216002019-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00429-19https://doaj.org/toc/2379-5042ABSTRACT 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. IMPORTANCE Streptococcus mutans is the major bacterium associated with dental caries. In order to thrive on the highly populated tooth surface and cause disease, S. mutans must be able to protect itself from hydrogen peroxide-producing commensal bacteria and compete effectively against the neighboring microbes. S. mutans produces mutacins, small antimicrobial peptides which help control the population of competing bacterial species. In addition, S. mutans produces a peptide called mutanobactin, which offers S. mutans 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 S. mutans.Katherine RaineyLandon WilsonStephen BarnesHui WuAmerican Society for MicrobiologyarticleStreptococcus mutansoxidative stressmutacinmutanobactinproteomicscompetitionMicrobiologyQR1-502ENmSphere, Vol 4, Iss 5 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Streptococcus mutans oxidative stress mutacin mutanobactin proteomics competition Microbiology QR1-502
spellingShingle	Streptococcus mutans oxidative stress mutacin mutanobactin proteomics competition Microbiology QR1-502 Katherine Rainey Landon Wilson Stephen Barnes Hui Wu Quantitative Proteomics Uncovers the Interaction between a Virulence Factor and Mutanobactin Synthetases in <italic toggle="yes">Streptococcus mutans</italic>
description	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. IMPORTANCE Streptococcus mutans is the major bacterium associated with dental caries. In order to thrive on the highly populated tooth surface and cause disease, S. mutans must be able to protect itself from hydrogen peroxide-producing commensal bacteria and compete effectively against the neighboring microbes. S. mutans produces mutacins, small antimicrobial peptides which help control the population of competing bacterial species. In addition, S. mutans produces a peptide called mutanobactin, which offers S. mutans 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 S. mutans.
format	article
author	Katherine Rainey Landon Wilson Stephen Barnes Hui Wu
author_facet	Katherine Rainey Landon Wilson Stephen Barnes Hui Wu
author_sort	Katherine Rainey
title	Quantitative Proteomics Uncovers the Interaction between a Virulence Factor and Mutanobactin Synthetases in <italic toggle="yes">Streptococcus mutans</italic>
title_short	Quantitative Proteomics Uncovers the Interaction between a Virulence Factor and Mutanobactin Synthetases in <italic toggle="yes">Streptococcus mutans</italic>
title_full	Quantitative Proteomics Uncovers the Interaction between a Virulence Factor and Mutanobactin Synthetases in <italic toggle="yes">Streptococcus mutans</italic>
title_fullStr	Quantitative Proteomics Uncovers the Interaction between a Virulence Factor and Mutanobactin Synthetases in <italic toggle="yes">Streptococcus mutans</italic>
title_full_unstemmed	Quantitative Proteomics Uncovers the Interaction between a Virulence Factor and Mutanobactin Synthetases in <italic toggle="yes">Streptococcus mutans</italic>
title_sort	quantitative proteomics uncovers the interaction between a virulence factor and mutanobactin synthetases in <italic toggle="yes">streptococcus mutans</italic>
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/dde0f3d3522949bab431a21cbcc21600
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Quantitative Proteomics Uncovers the Interaction between a Virulence Factor and Mutanobactin Synthetases in <italic toggle="yes">Streptococcus mutans</italic>

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