Quorum Sensing and Virulence Regulation in Commensal and Pathogenic Bacteria

Quorum sensing (QS) is a peptide-mediated bacterial communication process that regulates collective behaviors including genetic competence, biofilm formation, virulence, and horizontal gene transfer. In streptococci, QS commonly occurs through the ComABCDE and ComRS signaling pathways, which coordinate transcriptional responses through competence-associated regulators such as ComX. Although canonical models of streptococcal QS predict conserved activation of competence and virulence-associated phenotypes following pheromone induction, growing evidence suggests these systems exhibit substantial species-specific divergence. This dissertation investigates peptide-mediated QS regulation in commensal and opportunistic pathogenic streptococci, with particular emphasis on the development of synthetic QS modulators and the characterization of noncanonical signaling behaviors. Chapter 1 reviews the historical development of QS research and the mechanisms underlying peptide-mediated communication in streptococci, focusing on the ComABCDE and ComRS pathways, competence regulation, virulence-associated phenotypes, and advances in the rational design of peptide-based QS modulators. Next, chapter 2 describes the rational development of QS modulators targeting the competence regulon of Streptococcus constellatus, an opportunistic pathogen associated with severe pyogenic infections and abscess formation. Finally, chapter 3 investigates competence regulation in Streptococcus vestibularis, a member of the oral microbiome increasingly associated with systemic diseases including endocarditis, COPD, colorectal cancer, cirrhosis, type-two diabetes, and schizophrenia. This work expands current understanding of QS-mediated competence regulation, establishes new strategies for rational peptide-based modulation of bacterial signaling, and highlights the importance of species-specific investigation when developing anti-virulence therapeutic approaches targeting bacterial communication networks.

Level thesis:degree_level

Doctorate Degree

Year dc:date.issued

2026

Author dc:creator

• Rodriguez, Keely

Advisor dc:contributor.advisor

• Tal-Gan, Yftah

Committee members dc:contributor.committeemember

• Allan, Euan
• Sumby, Paul
• Jeffrey, Christopher
• Ryan, Robert

• bacteria
• peptides
• quorum sensing
• Streptococcus
• transformation
• virulence

Language dc:language.iso

en_US, English

Repository record dc:identifier.uri

https://scholarwolf.unr.edu/handle/11714/11945

OAI identifier oai:identifier

oai:scholarwolf.unr.edu:11714/11945