DMCA
Staphylococcus aureus Keratinocyte Invasion Is Dependent upon Multiple High-Affinity Fibronectin- Binding Repeats within FnBPA
| Citations: | 1 - 0 self |
BibTeX
@MISC{Edwards_staphylococcusaureus,
author = {Andrew M. Edwards and Ursula Potter and Nicola A. G. Meenan and Jennifer R. Potts and Ruth C. Massey},
title = {Staphylococcus aureus Keratinocyte Invasion Is Dependent upon Multiple High-Affinity Fibronectin- Binding Repeats within FnBPA},
year = {}
}
Share
 |
 |
 |
 |
||
OpenURL
Abstract
Staphylococcus aureus is a commensal organism and a frequent cause of skin and soft tissue infections, which can progress to serious invasive disease. This bacterium uses its fibronectin binding proteins (FnBPs) to invade host cells and it has been hypothesised that this provides a protected niche from host antimicrobial defences, allows access to deeper tissues and provides a reservoir for persistent or recurring infections. FnBPs contain multiple tandem fibronectin-binding repeats (FnBRs) which bind fibronectin with varying affinity but it is unclear what selects for this configuration. Since both colonisation and skin infection are dependent upon the interaction of S. aureus with keratinocytes we hypothesised that this might select for FnBP function and thus composition of the FnBR region. Initial experiments revealed that S. aureus attachment to keratinocytes is rapid but does not require FnBRs. By contrast, invasion of keratinocytes was dependent upon the FnBR region and occurred via similar cellular processes to those described for endothelial cells. Despite this, keratinocyte invasion was relatively inefficient and appeared to include a lag phase, most likely due to very weak expression of a5b1 integrins. Molecular dissection of the role of the FnBR region revealed that efficient invasion of keratinocytes was dependent on the presence of at least three high-affinity (but not low-affinity) FnBRs. Over-expression of a single highaffinity or three low-affinity repeats promoted invasion but not to the same levels as S. aureus expressing an FnBPA variant containing three high-affinity repeats. In summary, invasion of keratinocytes by S. aureus requires multiple high-affinity
Keyphrases
fnbr region multiple high-affinity fibronectin binding repeat keratinocyte invasion dependent endothelial cell efficient invasion staphylococcus aureus fnbpa variant protected niche initial experiment commensal organism frequent cause a5b1 integrins molecular dissection host antimicrobial defence high-affinity repeat serious invasive disease weak expression fibronectin binding protein multiple high-affinity similar cellular process fnbp function skin infection host cell single highaffinity soft tissue infection lag phase low-affinity repeat
