Kintarak, Sompid; (2003) Effects of staphylococcus aureus on human keratinocytes. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

In healing wounds, keratinocytes migrate on a fibronectin (FN)-rich granulation tissue and may phagocytose FN-coated wound debris. Staphylococcus aureus is a common infecting bacterium in wounds and heavy colonization of toxin- producing strain may cause mucosal damage. In addition, S. aureus can be internalized by non-phagocytic host cells thought to facilitate evasion of host cell immunity and antibiotics. The purpose of the experiments described in this thesis was to investigate the bacterial and host factors influencing the adhesion and internalization of S. aureus by human keratinocytes as well as the effects of S. aureus fibronectin-binding proteins (FnBPs) and its secreted products on keratinocyte functions. S. aureus FnBPs and host cell integrin 5 1 were important for the internalization of S. aureus by immortalized keratinocyte cell lines. However, in primary keratinocytes, S. aureus internalization occurred independently of FnBPs. In addition, purified S. aureus FnBP (rFnBPBDl-D4) had no effects on the adhesion and migration of primary keratinocytes on the fibronectin substrate, however it inhibited the migration of immortalized UP keratinocytes. Decreased UP cell migration in the presence of rFnBPBDl-D4 was not due to decrease in the adhesion or proliferation (BrdU incorporation) of the cells. The difference in the response of primary cells and cell lines to S. aureus may have important implications for the interpretation and translation of in vitro studies to predict in vivo responses. The effects of culture supernatants from S. aureus on keratinocyte functions were strain- and growth phase-dependent. The culture supernatants that contained undetectable toxins such as - and -toxin did not have any deleterious effects on keratinocytes. Toxin-containing supernatants, particularly a-toxin, from stationary growth phase of S. aureus inhibited the adhesion and migration of keratinocytes and increased cell death. S. aureus may gain access to the submucosal tissues by fatal damage of keratinocytes with its cytotoxins. The rFnBPBDl-D4 inhibited endogenous FN polymerization. Interaction of rFnBPBDl-D4 with intact and fragments of FN may influence cell behaviour.

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