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Updated: Feb 24, 2026
Staphylococcus aureus Growth using Human Hemoglobin as an Iron Source
Published on: February 7, 2013
Identification of Staphylococcus aureus Factors Required for Pathogenicity and Growth in Human Blood
John Connolly1, Emma Boldock1,2,3, Lynne R Prince3
1Department of Molecular Biology and Biotechnology, University of Sheffield, Sheffield, United Kingdom.
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.
Insights
Staphylococcus aureus requires specific genes for growth in human blood. Targeting the pabA gene and pyrimidine salvage pathway offers potential therapeutic strategies against this opportunistic pathogen.
Area of Science:
- Microbiology
- Pathogenesis
- Drug Discovery
Background:
- Staphylococcus aureus is a common human bacterium with significant pathogenic potential.
- S. aureus bacteremia frequently leads to poor patient outcomes.
- Identifying bacterial components essential for growth in human blood is crucial for developing new treatments.
Purpose of the Study:
- To identify Staphylococcus aureus genes essential for growth in human blood.
- To evaluate these genes as potential targets for novel antimicrobial therapies.
Main Methods:
- Screening of an ordered transposon mutant library of S. aureus.
- Identification of genes involved in hemolysis or growth on human blood agar.
- Validation of essential genes in a zebrafish embryo infection model.
Main Results:
- Nine genes were identified as critical for S. aureus growth or hemolysis in human blood.
- Three genes (purA, purB, pabA) were essential for pathogenesis in vivo.
- The pabA gene's growth defect was specific to red blood cells, linked to tetrahydrofolate biosynthesis and pyrimidine metabolism.
Conclusions:
- The pabA gene and the pyrimidine salvage pathway are potential therapeutic targets against S. aureus.
- A previously unrecognized human blood factor influences sulfonamide antibiotic efficacy.
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