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Gene Regulation in Microbial Communities: Quorum Sensing01:28

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Quorum sensing is a mechanism of bacterial communication that enables coordinated gene expression in response to changes in population density. This facilitates collective behaviors that enhance survival, resource acquisition, and ecological adaptation. This process relies on small signaling molecules called autoinducers that accumulate as bacterial populations grow. When a critical threshold concentration of autoinducers is reached, bacterial cells collectively modify gene expression,...
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Bacterial signaling can occur within bacteria (intracellular) or between bacteria (intercellular). At times, a group of bacteria behaves like a community. To achieve this, they engage in quorum sensing, the perception of higher cell density that causes changes in gene expression. Quorum sensing involves both extracellular and intracellular signaling. The signaling cascade starts with a molecule called an autoinducer (AI). Individual bacteria produce AIs that move out of the bacterial cell...
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Designing Highly Potent Side-Chain Lactam-Bridged Cyclic Competence-Stimulating Peptide-Based Quorum-Sensing

Uttam Ghosh1, Yftah Tal-Gan1

  • 1Department of Chemistry, University of Nevada, Reno, 1664 N. Virginia Street, Reno, Nevada 89557, United States.

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Summary

Researchers developed a novel cyclic peptide analogue of the competence stimulating peptide (CSP) from Streptococcus oligofermentans. This enhanced analogue combats Streptococcus mutans, a key cavity-causing bacterium, showing promise for dental caries prevention.

Keywords:
Streptococcus oligofermentansantivirulencecompetence stimulating peptideconformational screeningcyclic peptidesquorum sensing

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Area of Science:

  • Microbiology
  • Biochemistry
  • Drug Discovery

Background:

  • * Streptococcus oligofermentans, a beneficial oral bacterium, inhibits Streptococcus mutans, a primary cause of dental caries.
  • * This inhibition is linked to hydrogen peroxide production regulated by quorum sensing (QS).
  • * The competence stimulating peptide (CSP) is crucial for S. oligofermentans QS activation.

Purpose of the Study:

  • * To design and synthesize novel lactam-based cyclic analogues of the S. oligofermentans CSP signal.
  • * To enhance the biological activity and stability of the CSP signal for therapeutic applications.
  • * To explore the potential of these analogues in combating dental caries.

Main Methods:

  • * Performed a ring position scan to identify optimal sites for macrolactamization within the CSP sequence.
  • * Conducted systematic scans of ring size and bridge position to optimize cyclic peptide conformation.
  • * Synthesized and evaluated the biological activity and enzymatic stability of the resulting cyclic analogues.

Main Results:

  • * Identified a highly active cyclic analogue, CSP-cyc(K2E2), which is 7-fold more potent than the native CSP.
  • * Demonstrated improved stability of the cyclic analogue against enzymatic degradation.
  • * Confirmed the potential of CSP-cyc(K2E2) as a chemical probe and therapeutic agent.

Conclusions:

  • * Novel cyclic CSP analogues were successfully developed, with CSP-cyc(K2E2) showing superior activity and stability.
  • * These findings highlight the potential of cyclic CSP analogues to enhance the biotherapeutic efficacy of S. oligofermentans.
  • * The developed analogue offers a promising strategy for controlling S. mutans and preventing dental caries.