Control of streptokinase gene expression in group A & C streptococci by two-component regulators.

BACKGROUND & OBJECTIVES Group A streptococci (GAS) and human isolates of group C streptococci (GCS) have the stable capacity to produce the plasminogen activator streptokinase, albeit with varying efficiency. This property is subject to control by two two-component regulatory systems, FasCAX and CovRS, which act as activator and repressor, respectively. The present work aims at balancing these opposing activities in GAS and GCS, and at clarifying the phylogenetic position of the FasA response regulator, the less understood regulator of the two systems. METHODS The GCS strain H46A and GAS strain NZ131 were used. Escherichia coli JM 109 was used as host for plasmid construction. Streptokinase activity of various wild type and mutant strains was measured. Phylogenetic trees of streptococcal FasA homologues were established. RESULTS The streptokinase activities of the GAS strain NZ131 and the GCS strain H46A were attributable to more efficient CovR repressor action in NZ131 than in H46A. The FasA activator, on the other hand, functioned about equally efficient in the two strains. Phylogenetically, FasA homologues clustered distinctly in the proposed FasA-BlpR-ComE family of streptococcal response regulators and used the LytTR domain for DNA binding. INTERPRETATION & CONCLUSION Assessing the apparent streptokinase activity of streptoccal strains require the dissection of the activities of the cov and fas systems. Although experimental evidence is still missing, FasA is closely related to a widely distributed family of streptococcal response regulators that is involved in behavioral processes, such as quorum sensing.