Pharmaceutical Sciences ETDs

Publication Date

Winter 1-31-2022

Abstract

Staphylococcus aureus is a pathogenic bacteria that causes significant morbidity and mortality. As antibiotic resistance by S. aureus continues to be a serious concern, developing novel drug therapies to combat these infections is vital. Quorum sensing inhibitors (QSI) dampen S. aureus virulence and facilitate clearance by the host immune system by blocking quorum sensing signaling that promotes upregulation of the accessory gene regulator (agr) operon. While QSIs have shown therapeutic promise in mouse models of S. aureus infection, their further development has been hampered by the suggestion that agr inhibition promotes biofilm formation. In these studies, we investigated the relationship between agr function and biofilm growth across various S. aureus strains and experimental conditions, including in a mouse model of implant associated infection. We found that agr deletion was associated with increased biofilm only under narrow in vitro conditions and, crucially, was not associated with enhanced biofilm development in vivo.

Fourth Committee Member

Graham Timmins

Fifth Committee Member

Alexander Horswill

First Committee Member (Chair)

Pamela Hall

Degree Name

Pharmaceutical Sciences

Second Committee Member

Seth Daly

Level of Degree

Masters

Third Committee Member

Renee-Claude Mercier

Department Name

College of Pharmacy

Document Type

Thesis

Download

Share

COinS