Opacity Factor Activity and Epithelial Cell Binding by the SerumOpacity Factor Protein of Streptococcus pyogenes Are Functionally Discrete*□S

Serum opacity factor (SOF) is a unique multifunctional viru-lence determinant expressed at the surface ofStreptococcus pyo-genes and has been shown to elicit protective immunity against GAS infection in amurine challengemodel. SOF consists of two distinct domains with different binding capacities: an N-termi-nal domain that binds apolipoprotein AI and a C-terminal repeat domain that binds fibronectin and fibrinogen. The capacity of SOF to opacify serum by disrupting the structure of high density lipoproteins may preclude its use as a vaccine anti-gen in humans. This study generated mutant forms of recombi-nant SOF with reduced (100-fold) or abrogated opacity factor (OF) activity, for use as vaccine antigens. However, alterations introduced into the N-terminal SOF peptide (SOFFn) by mutagenesis to abrogateOF activity, abolish the capacity of SOF to protect against lethal systemic S. pyogenes challenge in