Elucidating the Mechanisms of Persister Formantion in Staphylococcus aureus

Abstract

What Causes Chronic Infections?: Mechanisms of Antibiotic Tolerance in Staphylococcus aureus Staphylococcus aureus (S. aureus), a Gram positive bacterium, is a leading cause of hospital-acquired infections. It has developed resistance to most antibiotics in current use, meaning there is a need for novel treatment options. Resistance aside, when strains are susceptible to the antibiotic being used in treatment, S. aureus infections are still extremely difficult to treat. Despite the apparent susceptibility to a given antibiotic, clearing the infection completely is a difficult process and chronic or re-current infections are quite common. Persister cells are a sub-population of bacteria that exhibit extremely high tolerance to bactericidal activity of antibiotics. S. aureus have been shown, in vitro, to produce a relatively high number of persister cells in exponential growth phase relative to the gram negative organisms Escherichia coli and Pseudomonas aeruginosa and remarkably, in stationary phase, the entire S. aureus population appears to consist of persister cells. It is reasonable to assume that the high persister levels in S. aureus and the difficulty in treating infections are related. Little is known about the mechanisms behind persister formation in S. aureus. The first step to elucidating the molecular mechanisms would be to look at which biological pathways are involved. To do this I will sort cells using fluorescently labeled proteins to identify which, if any, genes are upregulated in persisters compared to sensitive cells. Additionally, I will use clinical isolates to look for genetic mutations that lead to increased persistence and chronic infection.