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- Title
Staphylococcus aureus keratinocyte invasion is mediated by integrin-linked kinase and Rac1.
- Authors
Sayedyahossein, Samar; Xu, Stacey X.; Rudkouskaya, Alena; McGavin, Martin J.; McCormick, John K.; Dagnino, Lina
- Abstract
Staphylococcus aureus is a major component of the skin microbiota and causes a large number of serious infections. S. aureus first interacts with epidermal kerati-nocytes to breach the epidermal barrier through mechanisms not fully understood. By use of primary keratinocytes from mice with epidermis-restricted Ilk gene inactivation and control integrin-linked kinase (ILK)-expressing litter-mates, we investigated the role of ILK in epidermal S. aureus invasion. Heat-killed, but not live, bacteria were internalized to Rab5- and Rab7-positive phagosomes, and incubation with keratinocyte growth factor increased their uptake 2.5-fold. ILK-deficient mouse keratinocytes internalized bacteria 2- to 4-fold less efficiently than normal cells. The reduced invasion by live S. aureus of ILK-deficient cells was restored in the presence of exogenous, constitutively active Rac1. Thus, Rac1 functions downstream from ILK during invasion. Further, invasion by S. aureus of Rac1-deficient cells was 2.5-fold lower than in normal cells. Paradoxically, staphylococcal cutaneous penetration of mouse skin explants with ILK-deficient epidermis was 35-fold higher than that of normal skin, indicating defects in epidermal barrier function in the absence of ILK. Thus, we identified an ILK-Rac1 pathway essential for bacterial invasion of keratinocytes, and established ILK as a key contributor to prevent invasive staphylococcal cutaneous infection.
- Subjects
STAPHYLOCOCCUS aureus; KERATINOCYTES; EPIDERMIS; INTEGRIN-linked kinase; SERINE/THREONINE kinases
- Publication
FASEB Journal, 2015, Vol 29, Issue 2, p711
- ISSN
0892-6638
- Publication type
Article
- DOI
10.1096/fj.14-262774