Regulation of weak acid-dependent cell death by the msaABCR operon during biofilm formation of Staphylococcus aureus
Date of Award
Honors College Thesis
Biological Sciences BS
Biological Sciences; Foreign Languages and Literature
Mohamed Elasri, Ph.D
Staphylococcus aureus is a dangerous human pathogen and a leading cause of both nosocomial and community-associated infections. Infection by S. aureus is a growing health concern due to the emergence of antibiotic resistance and the capability to form robust biofilms. Major constituents of the biofilm extracellular matrix are demonstrated to be released via controlled autolysis of a subpopulation of the biofilm. As indicated in past studies, the programmed cell death (PCD) of S. aureus grown in a biofilm microenvironment is potentiated by the buildup of acetate, a byproduct of glucose metabolism, which causes cytoplasmic acidification. Furthermore, it has been shown that the use of antibiotics in low doses stimulates biofilm formation by inducing autolysis. Our lab has recently shown that the deletion of the msaABCR operon in S. aureus causes a decrease of biofilm thickness and an increase of dead cell biomass in the biofilm relative to wild-type (WT). However, the precise mechanism is still largely unknown. I hypothesized that msaABCR plays an important role in antibiotic- and glucose-induced biofilm formation by regulating cell death in S. aureus. To investigate this, I performed biofilm assays in a msaABCR mutant with the addition of vancomycin. I also performed late-stationary phase survival assays and measured the rate of acetate production in excess glucose medium. Indeed, the results show that vancomycin is not able to induce biofilm formation in the msaABCR mutant and that the mutant exhibits an increased rate of cell death relative to WT under excess glucose conditions. Furthermore, acetate production was increased in the mutant with excess glucose relative to WT. These results suggest uncontrolled weak acid-dependent cell death in the msaABCR mutant.
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Polley, Sarah-Elizabeth M., "Regulation of weak acid-dependent cell death by the msaABCR operon during biofilm formation of Staphylococcus aureus" (2020). Honors Theses. 751.