Staphylococcus aureus extracellular adherence protein triggers TNFα release, promoting attachment to endothelial cells via protein A.
Staphylococcus aureus is a leading cause of bacteraemia, which frequently results in complications such as infective endocarditis, osteomyelitis and exit from the bloodstream to cause metastatic abscesses. Interaction with endothelial cells is critical to these complications and several bacterial proteins have been shown to be involved. The S. aureus extracellular adhesion protein (Eap) has many functions, it binds several host glyco-proteins and has both pro- and anti-inflammatory activity. Unfortunately its role in vivo has not been robustly tested to date, due to difficulties in complementing its activity in mutant strains. We previously found Eap to have pro-inflammatory activity, and here show that purified native Eap triggered TNFα release in whole human blood in a dose-dependent manner. This level of TNFα increased adhesion of S. aureus to endothelial cells 4-fold via a mechanism involving protein A on the bacterial surface and gC1qR/p33 on the endothelial cell surface. The contribution this and other Eap activities play in disease severity during bacteraemia was tested by constructing an isogenic set of strains in which the eap gene was inactivated and complemented by inserting an intact copy elsewhere on the bacterial chromosome. Using a murine bacteraemia model we found that Eap expressing strains cause a more severe infection, demonstrating its role in invasive disease.
Department of Biology and Biochemistry, University of Bath, Bath, United Kingdom.
Andrew M
AM
Edwards
Maria Gabriela
MG
Bowden
Eric L
EL
Brown
Maisem
M
Laabei
Ruth C
RC
Massey
D018829:Adhesins, Bacterial; D000818:Animals; D001422:Bacterial Adhesion; D001426:Bacterial Proteins / Q000378:metabolism; D002876:Chromosomes, Bacterial; D004305:Dose-Response Relationship, Drug; D004696:Endocarditis / Q000382:microbiology; D015964:Gene Expression Regulation, Bacterial; D005816:Genetic Complementation Test; D006801:Humans; D007249:Inflammation; D051379:Mice; D010019:Osteomyelitis / Q000382:microbiology; D016601:RNA-Binding Proteins / Q000378:metabolism; D013203:Staphylococcal Infections / Q000382:microbiology; D013205:Staphylococcal Protein A / Q000378:metabolism; D013211:Staphylococcus aureus / Q000378:metabolism*; D013234:Stem Cells; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D037521:Virulence Factors
D018829:Adhesins, Bacterial; D001426:Bacterial Proteins; C444739:Eap-N protein, Staphylococcus aureus; D016601:RNA-Binding Proteins; D013205:Staphylococcal Protein A; D014409:Tumor Necrosis Factor-alpha; D037521:Virulence Factors