PUBLICATION
The identification of Staphylococcus aureus factors required for pathogenicity and growth in human blood
- Authors
- Connolly, J., Boldock, E., Prince, L.R., Renshaw, S.A., Whyte, M.K., Foster, S.J.
- ID
- ZDB-PUB-170817-12
- Date
- 2017
- Source
- Infection and Immunity 85(11): (Journal)
- Registered Authors
- Renshaw, Steve A.
- Keywords
- none
- MeSH Terms
-
- Embryo, Nonmammalian
- Gene Expression Regulation, Bacterial*
- Mice, Inbred BALB C
- Survival Analysis
- Virulence
- Disease Models, Animal
- Blood Cells/microbiology
- Virulence Factors/genetics*
- Virulence Factors/metabolism
- Host-Pathogen Interactions/immunology
- Adenylosuccinate Synthase/genetics
- Adenylosuccinate Synthase/metabolism
- Sheep
- Bacterial Proteins/genetics*
- Bacterial Proteins/metabolism
- Zebrafish
- Animals
- Mice
- Staphylococcus aureus/genetics*
- Staphylococcus aureus/metabolism
- Staphylococcus aureus/pathogenicity*
- Humans
- Staphylococcal Infections/immunology*
- Staphylococcal Infections/microbiology
- Staphylococcal Infections/mortality
- Adenylosuccinate Lyase/genetics
- Adenylosuccinate Lyase/metabolism
- Culture Media/chemistry
- DNA Transposable Elements
- Horses
- PubMed
- 28808156 Full text @ Infect. Immun.
Citation
Connolly, J., Boldock, E., Prince, L.R., Renshaw, S.A., Whyte, M.K., Foster, S.J. (2017) The identification of Staphylococcus aureus factors required for pathogenicity and growth in human blood. Infection and Immunity. 85(11).
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping