Genetic organisation of the M protein region in human isolates of group C and G streptococci: two types of multigene regulator-like (mgrC) regions

In addition to beta-haemolytic streptococci belonging to Lancefield group A (Streptococcus pyogenes, GAS), human isolates of group C (GCS) and group G (GGS) streptococci (S. dysgalactiae subsp. equisimilis:) have been implica ted as causative agents in outbreaks of purulent pharyngitis, of wound infe ctions and recently also of streptococcal toxic shock-like syndrome. Very l ittle is known about the organisation of the genomic region in which the em m gene of GCS and GCS is located. We have investigated the genome sequences flanking the emm gene in GCS by sequencing neighbouring fragments obtained by inverse PCR. Our sequence data for GCS strains 25287 and H46A revealed two types of arrangement in the emm region, which differ significantly from the known types of mga regulon in GAS. We named this segment of the genome mgrC (for multigene regulon-like segment in group C streptococci). In stra ins belonging to the first mgrC type (prototype strain 25287) the emm gene is flanked upstream by mgc, a gene that is 61% identical to the mga gene of GAS. A phylogenetic analysis of the deduced protein sequences showed that Mgc is related to Mga proteins of various types of GAS but forms a distinct cluster. Downstream of emm, the mgrC sequence region is bordered by rel. T his gene encodes a protein that functions in the synthesis and degradation of guanosine 3',5' bipyrophosphate (ppGpp) during the stringent regulatory response to amino acid deprivation. In the second mgrC type (prototype stra in H46A), the genes mgc and emm are arranged as in type 1. But an additiona l ORF (orf) is inserted in opposite orientation between emm and rel. This o rf shows sequence homology to cpdB, which is present in various microorgani sms and encodes 2',3' cyclo-nucleotide 2'-phosphodiesterase. PCR analysis s howed that these two mgrC arrangements also exist in GGS. Our sequence and PCR data further showed that both types of mgrC region in GCS and GGS are l inked via rel to the streptokinase region characterised recently in strain H46A. A gene encoding C5a peptidase, which is present at the 3' end of the mga regulon in GAS, was not found in the mgrC region identified in the GCS and GGS strains investigated here.