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Generation of a Gene-disrupted Streptococcus mutans Strain Without Gene Cloning
Published on: October 23, 2017
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Caries-Associated Biosynthetic Gene Clusters in Streptococcus mutans
S S Momeni1, S M Beno2, J L Baker3
1Department of Pediatric Dentistry, University of Alabama at Birmingham, Birmingham, AL, USA.
Journal of Dental Research
|April 17, 2020
Summary
New biosynthetic gene clusters (BGCs) in Streptococcus mutans were identified and linked to early childhood caries (ECC). These novel butyrolactone-ladderane-like BGCs (BL-BGCs) are highly expressed in caries subjects and associated with increased acid production, a key cariogenic feature.
Area of Science:
- Microbiology and Oral Health
- Genomics and Bioinformatics
- Biochemistry and Molecular Biology
Background:
- Early childhood caries (ECC) is a global oral health issue, primarily driven by cariogenic bacteria like Streptococcus mutans.
- Biosynthetic gene clusters (BGCs) in microbes produce small molecules that can influence disease development, including dental caries.
- Understanding the genetic basis of S. mutans virulence is crucial for developing targeted interventions against ECC.
Purpose of the Study:
- To identify and characterize BGCs in S. mutans isolates from a high-risk ECC population.
- To assess the association of identified BGCs with ECC prevalence and cariogenic potential.
- To investigate the functional role of novel BGCs in S. mutans virulence using in vitro models.
Main Methods:
- Whole-genome sequencing of 40 S. mutans isolates from a high-caries risk pediatric cohort.
- Bioinformatic analysis using antiSMASH to identify BGCs, including novel butyrolactone-like, ladderane-like, and hybrid BL-BGCs.
- Cross-referencing with transcriptomics data, PCR screening, and in vitro biofilm assays with deletion mutants.
Main Results:
- A total of 252 BGCs were identified, including three novel types: butyrolactone-like, ladderane-like, and BL-BGCs.
- BL-BGCs were highly expressed in caries subjects and present in 93% of children with ECC.
- Deletion of BL-BGCs increased biofilm pH but did not alter other virulence factors; BL-BGC strains produced more acid and less biofilm.
Conclusions:
- This study reports the novel finding and clinical significance of BL-BGCs in S. mutans associated with ECC.
- BL-BGCs appear to play a critical role in S. mutans-mediated cariogenicity, particularly in acid production.
- Further research is needed to elucidate the structure and function of BL-BGC metabolites and their precise mechanism in caries development.
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