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Intermedilysin release by Streptococcus intermedius: effects of various antibacterial drugs at sub-MIC levels
Mark B Taylor1, Janice H L Oh, K L Kang
1Department of Microbiology, National University of Singapore, Blk MD4, 5 Science Drive 2, Singapore 117597, Singapore. micmbt@nus.edu.sg
Abstract:
Intermedilysin is a cytolytic toxin produced by Streptococcus intermedius, a pathogen of humans. In vitro studies showed that exposure of S. intermedius to sub-minimum inhibitory concentration (MIC) levels (1/2 MIC) of protein-inhibiting antibiotics and nucleic acid-inhibiting antibiotics decreased intermedilysin release by S. intermedius. The most potent antibiotic was clindamycin. On the other hand, exposure to cell wall-inhibiting antibiotics generally showed insignificant changes in intermedilysin release at sub-MIC concentrations. Investigations into possible mechanisms underlying this sub-MIC effect with clindamycin showed that there was selective decrease in biosynthesis and release of toxin after exposure to 1/2 MIC condition. However, no significant differences in the mRNA levels of the intermedilysin gene were observed.
Insights
Certain antibiotics, like clindamycin, significantly reduce the release of intermedilysin, a toxin from Streptococcus intermedius, by inhibiting its biosynthesis. This finding offers potential new strategies for managing infections caused by this human pathogen.
Area of Science:
- Microbiology
- Infectious Diseases
- Pharmacology
Background:
- Streptococcus intermedius is a human pathogen that produces intermedilysin, a cytolytic toxin.
- Understanding factors that regulate intermedilysin release is crucial for developing strategies against S. intermedius infections.
Purpose of the Study:
- To investigate the effect of sub-minimum inhibitory concentrations (sub-MICs) of various antibiotics on intermedilysin release by S. intermedius.
- To explore the potential mechanisms behind antibiotic-mediated modulation of intermedilysin production.
Main Methods:
- Exposure of S. intermedius cultures to sub-MIC levels (1/2 MIC) of different classes of antibiotics.
- Quantification of intermedilysin release into the culture supernatant.
- Analysis of toxin biosynthesis and gene expression (mRNA levels) following antibiotic treatment.
Main Results:
- Protein-inhibiting and nucleic acid-inhibiting antibiotics significantly decreased intermedilysin release.
- Clindamycin demonstrated the most potent inhibitory effect on intermedilysin release at sub-MIC levels.
- Cell wall-inhibiting antibiotics showed minimal impact on intermedilysin release.
- Clindamycin exposure selectively reduced intermedilysin biosynthesis and release without altering mRNA levels of the intermedilysin gene.
Conclusions:
- Sub-MIC concentrations of specific antibiotics, particularly clindamycin, can effectively reduce intermedilysin release from S. intermedius.
- The mechanism involves decreased toxin biosynthesis rather than transcriptional regulation of the intermedilysin gene.
- These findings suggest a potential therapeutic approach for managing S. intermedius infections by modulating toxin production.
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