vicR overexpression in Streptococcus mutans causes aggregation and affects interspecies competition

Area of Science:

• Microbiology
• Molecular Biology
• Oral Health

Background:

• Streptococcus mutans is a primary cause of dental caries.
• The VicRK two-component signal transduction system (TCSTS) in S. mutans modulates virulence factors including biofilm formation and acid resistance.
• VicRK also influences mutacin production via the ComDE TCSTS.

Purpose of the Study:

• To investigate the role of VicR, a component of the VicRK TCSTS, in S. mutans virulence and cell morphology.
• To elucidate the regulatory mechanisms of VicR on biofilm formation, mutacin production, and interspecies competition.
• To determine if VicR directly regulates the expression of mutacin genes.

Main Methods:

• Overexpression of vicR in S. mutans.
• Analysis of biofilm formation and cell chain length.
• Gene expression analysis using transcriptional profiling.
• Bacterial competition assays against Streptococcus gordonii and Streptococcus sanguinis.
• Electrophoretic mobility shift assays (EMSA) and DNase I footprinting assays to assess direct DNA binding.

Main Results:

• Overexpression of vicR led to increased cell aggregation, abnormal biofilm formation, and longer bacterial chains.
• Mutacin gene expression, including nlmA, nlmB, nlmC, and nlmD, was upregulated in the vicR-overexpressing strain, particularly under aerobic conditions.
• The vicR-overexpressing strain exhibited enhanced competitiveness against S. gordonii, and this correlation was observed in clinical isolates.
• VicR was confirmed to directly bind to the promoter region of the nlmD gene.

Conclusions:

• The VicRK TCSTS plays a significant role in regulating S. mutans cell morphology and biofilm development.
• VicRK controls mutacin production in S. mutans, with oxygen levels influencing this regulation.
• VicR directly targets the nlmD gene promoter, thereby regulating the production of mutacin NlmD and influencing interspecies competition.