3 DIFFERENT TYPES OF ORGANIZATION OF THE VIR REGULON IN GROUP-A STREPTOCOCCI

The DNA of group A streptococci (GAS) encodes several important virulence factors such as the antiphagocytic M. protein, the Ig-Fc-binding M-related proteins (FcrA-like and EnnX-like) and the complement factor-inactivating C5a peptidase. The corresponding genes emm, fcrA, ennX, and scpA, respectively, were assumed to be located close together in the GAS genome. Additionally, emm and scpA have been. found to be under the positive, coordinate control of the virR locus, which led to the designation ''vir regulon'' for the corresponding genomic segment. In order to map the vir regulons of many GAS serotypes and to analyse any correlation between the organization of vir regulons and circumscribed heterogeneities within the emm, virR, and scpA genes, an approach using several distinct sets of polymerase chain reaction (PCR) experiments was chosen. By examination of the genomic DNA of 42 GAS isolates from 36 different M serotypes three patterns of vir regulon topography were found. The first, designated ''large vir regulon'' (LVR), consists of virR-fcrA(-like) - emm - ennX(-like) - scpA. The second, designated ''small vir regulon'' (SVR), contains virR - emm - scpA, and the last, designated ''unusual vir regulon'' (UVR), resembles SVR but contains additional heterogeneous sequences between emm and scpA. The patterns correlate with heterogeneities at the 3' ends of the virR and scpA genes, with the M classification system and the occurrence of specific non-coding intervening sequences within the vir regulons. The potential impact of these patterns on models to account for generation of vir regulons is discussed.