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Exploiting Conserved Quorum Sensing Signals in Streptococcus mutans and Streptococcus pneumoniae
Giulia Bernabè1, Anthony Pauletto1, Annj Zamuner2
1Department of Molecular Medicine, Section of Microbiology, University of Padova, Via A. Gabelli 63, 35127 Padova, Italy.
Microorganisms
|December 23, 2022
Summary
New synthetic analogs of Streptococcus pneumoniae competence stimulating peptide (CSP) effectively inhibit Streptococcus mutans virulence factors. These compounds offer potential for novel therapeutic strategies targeting complex oral microbiota infections.
Area of Science:
- Microbiology
- Molecular Biology
- Biochemistry
Background:
- Streptococcus species can be commensal or pathogenic, with virulence often regulated by quorum sensing (QS).
- Streptococcus mutans and Streptococcus pneumoniae share homologous QS systems and competence stimulating peptide (CSP) signaling pathways.
- The interplay between S. mutans and S. pneumoniae in microbial communities suggests a role for QS-mediated fratricide.
Purpose of the Study:
- To design and synthesize analogs of S. pneumoniae CSP to inhibit QS in S. mutans.
- To investigate the impact of these analogs on S. mutans virulence factors, including biofilm formation and bacteriocin production.
- To identify specific modifications in CSP sequences that confer potent quorum-quenching activity.
Main Methods:
- Synthesis of modified S. pneumoniae CSP analogs.
- Assay of CSP analog effects on S. mutans gene expression related to QS and biofilm formation.
- Evaluation of CSP analog impact on S. mutans bacteriocin production in co-culture experiments.
Main Results:
- S. pneumoniae CSP analogs significantly reduced S. mutans QS gene expression and biofilm formation without affecting bacterial growth.
- The synthesized CSP analogs inhibited bacteriocin production by S. mutans.
- The CSP analog CSP1AA, with modifications in receptor recognition residues, exhibited the most potent quorum-quenching activity.
Conclusions:
- Modified S. pneumoniae CSPs can selectively inhibit virulence in S. mutans, highlighting the potential for QS-targeted therapies.
- Specific chemical modifications in CSP sequences are crucial for controlling inter-species communication and virulence in complex microbial communities.
- These findings open avenues for developing novel therapeutic interventions against virulence factors in the oral microbiota.
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