Identification of Staphylococcus aureus factors required for pathogenicity and growth in human blood

Connolly, J., Boldock, E., Prince, L. R., Renshaw, S. A., Whyte, M. K., Foster, S. J. and Pirofski, L.-a. (2017) Identification of Staphylococcus aureus factors required for pathogenicity and growth in human blood. Infection and Immunity, 85(11), e00337-17. (doi: 10.1128/IAI.00337-17) (PMID:28808156) (PMCID:PMC5649012)

Abstract

Staphylococcus aureus is a human commensal but also has devastating potential as an opportunistic pathogen. S. aureus bacteremia is often associated with an adverse outcome. To identify potential targets for novel control approaches, we have identified S. aureus components that are required for growth in human blood. An ordered transposon mutant library was screened, and 9 genes involved specifically in hemolysis or growth on human blood agar were identified by comparing the mutants to the parental strain. Three genes (purA, purB, and pabA) were subsequently found to be required for pathogenesis in the zebrafish embryo infection model. The pabA growth defect was specific to the red blood cell component of human blood, showing no difference from the parental strain in growth in human serum, human plasma, or sheep or horse blood. PabA is required in the tetrahydrofolate (THF) biosynthesis pathway. The pabA growth defect was found to be due to a combination of loss of THF-dependent dTMP production by the ThyA enzyme and increased demand for pyrimidines in human blood. Our work highlights pabA and the pyrimidine salvage pathway as potential targets for novel therapeutics and suggests a previously undefined role for a human blood factor in the activity of sulfonamide antibiotics.

• Item Type: Articles
• Additional Information: This work was funded by the Wellcome Trust (grants 099957/Z/12/Z and 089981) and the University of Sheffield 2022 Futures program
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Connolly, Mr John
• Authors: Connolly, J., Boldock, E., Prince, L. R., Renshaw, S. A., Whyte, M. K., Foster, S. J., and Pirofski, L.-a.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Infection and Immunity
• Publisher: American Society for Microbiology
• ISSN: 0019-9567
• ISSN (Online): 1098-5522
• Published Online: 14 August 2017
• Copyright Holders: Copyright © 2017 Connolly et al.
• First Published: First published in Infection and Immunity 85(11):e00337-17
• Publisher Policy: Reproduced under a Creative Commons License