STREPTOCOCCUS-PYOGENES TYPE-IIA IGG FC RECEPTOR EXPRESSION IS CO-ORDINATELY REGULATED WITH M-PROTEIN AND STREPTOCOCCAL C5A-PEPTIDASE

Streptococcus pyogenes is an important agent of human disease which expresses a variety of proteins and polysaccharides on its surface. Surface molecules M protein and streptococcal C5a peptidase (SCPA) are virulence factors which undergo concurrent phase variation and are under the co-ordinate control of the virR locus. Most opacity factor-positive (OF+) strains of S. pyogenes also express IgG Fc receptor proteins on their surface. These studies were initiated to determine whether the type IIa Fc receptor on the surface of S. pyogenes phase-varies with members of this regulatory circuit. Several methods were applied to M(+) and M(-) variant strains to evaluate this question. (i) Immunoblot assays quantified Fc receptors on whole cells by using human IgG myeloma protein and receptor-specific antibody. M(+) strains bound IgG and antibody specific for Fc protein, whereas M(-) strains did not. (ii) Enzyme-linked immunosorbent assays quantified Fc receptor antigen expression and showed that M(+) strains produce more Fc receptor protein than their M(-) derivatives. (iii) Quantitative RNA dot blots showed that the message for the Fc receptor gene (fcrA) was reduced in M(-) strains. RNA from M(+) strains hybridized to the fcrA probe at a greater dilution than that from their M(-) counterparts. (iv) Northern hybridization showed that the fcrA transcript is 1200 nucleotides in size and distinct from transcripts for M and SCPA proteins. These data are evidence for the co-ordinate transcriptional control of the Fc receptor, M protein, and SCPA and show that these proteins co-ordinately phase-vary within the same regulatory circuit.