Role of Streptococcal T Antigens in Superficial Skin Infection

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Abstract
FCT region genes of Streptococcus pyogenes encode surface proteins that include f ibronectin- and c ollagen-binding proteins and the serological markers known as T antigens, some of which give rise to pilus-like appendages. It remains to be established whether FCT region surface proteins contribute to virulence by in vivo models of infection. In this study, a highly sensitive and ecologically relevant humanized mouse model was used to measure superficial skin infection. Three genes encoding FCT region surface proteins essential for T-serotype specificity were inactivated. Both the Δ cpa and Δ prtF2 mutants were highly attenuated for virulence when topically applied to the skin following exponential growth but were fully virulent when delivered in stationary phase. In contrast, the Δ fctA mutant was virulent at the skin, regardless of its initial growth state. Immunoblots of cell extracts revealed anti-FctA-reactive, ladder-like polymers characteristic of streptococcal pili. In addition, FctA formed a heteropolymer with the putative collagen-binding protein Cpa. The Δ fctA mutant showed a loss in anti-Cpa-reactive polymers, whereas anti-FctA-reactive polymers were reduced in the Δ cpa mutant. The findings suggest that both FctA and Cpa are required for pilus formation, but importantly, an intact pilus is not essential for Cpa-mediated virulence. Although it is an integral part of the T-antigen complex, the fibronectin-binding protein PrtF2 is not covalently linked to the FctA- and Cpa-containing heteropolymer derived from cell extracts. The data provide direct evidence that streptococcal T antigens function as virulence factors in vivo, but they also reveal that a pilus-like structure is not essential for the most common form of streptococcal skin disease.