Screening for purine transporters in S. aureus
Abstract
Staphylococcus aureus is an important human pathogen and crucial part of its pathogenesis depends on its ability to acquire purines to cause disease. In this study, I screened a library of individual mutants under purine import-dependent conditions by inhibiting the purine biosynthesis using the pharmacological agents methotrexate and 6-mercaptopurine and supplementing inosine monophosphate and/or guanine as an exogenous purine source. I identified an ATP-Binding Cassette transporter mutant that failed to grow under the selective purine transport conditions. Further growth characterization of the mutant revealed that the growth defect was not due to an inability to transport purines but rather to downstream effects related to the toxicity of the purine biosynthesis inhibitors. A thorough understanding of S. aureus purine acquisition will allow for development of antimicrobials with prolonged effectiveness.