Pleiotropic Regulation of Virulence Genes in Streptococcus mutans by the Conserved Small Protein SprV.
Streptococcus mutans, an oral pathogen associated with dental caries, colonizes tooth surfaces as polymicrobial biofilms known as dental plaque.S. mutansexpresses several virulence factors that allow the organism to tolerate environmental fluctuations and compete with other microorganisms. We recently identified a small hypothetical protein (90 amino acids) essential for the normal growth of the bacterium. Inactivation of the gene, SMU.2137, encoding this protein caused a significant growth defect and loss of various virulence-associated functions. AnS. mutansstrain lacking this gene was more sensitive to acid, temperature, osmotic, oxidative, and DNA damage-inducing stresses. In addition, we observed an altered protein profile and defects in biofilm formation, bacteriocin production, and natural competence development, possibly due to the fitness defect associated with SMU.2137 deletion. Transcriptome sequencing revealed that nearly 20% of theS. mutansgenes were differentially expressed upon SMU.2137 deletion, thereby suggesting a pleiotropic effect. Therefore, we have renamed this hitherto uncharacterized gene assprV(streptococcalpleiotropicregulator ofvirulence). The transcript levels of several relevant genes in thesprVmutant corroborated the phenotypes observed uponsprVdeletion. Owing to its highly conserved nature, inactivation of thesprVortholog inStreptococcus gordoniialso resulted in poor growth and defective UV tolerance and competence development as in the case ofS. mutansOur experiments suggest that SprV is functionally distinct from its homologs identified by structure and sequence homology. Nonetheless, our current work is aimed at understanding the importance of SprV in theS. mutansbiology.IMPORTANCEStreptococcus mutansemploys several virulence factors and stress resistance mechanisms to colonize tooth surfaces and cause dental caries. Bacterial pathogenesis is generally controlled by regulators of fitness that are critical for successful disease establishment. Sometimes these regulators, which are potential targets for antimicrobials, are lost in the genomic context due to the lack of annotated homologs. This work outlines the regulatory impact of a small, highly conserved hypothetical protein, SprV, encoded byS. mutansWe show that SprV affects the transcript levels of various virulence factors required for normal growth, biofilm formation, stress tolerance, genetic competence, and bacteriocin production.
Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City, Kansas, USA.
Manoharan
M
Shankar
Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City, Kansas, USA.
Mohammad S
MS
Hossain
Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City, Kansas, USA ibiswas@kumc.edu.
Indranil
I
Biswas
D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D018441:Biofilms / Q000254:growth & development; D017124:Conserved Sequence; D004269:DNA, Bacterial / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology*; D016680:Genome, Bacterial; D009154:Mutation; D013295:Streptococcus mutans / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D013312:Stress, Physiological; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
D001426:Bacterial Proteins; D004269:DNA, Bacterial; D037521:Virulence Factors
Streptococcus mutans; bacteriocins; biofilms; global virulence; pleiotropic regulator; stress response