In contrast to the M49 strain, where Nra acts as a negative regulator of pilus gene transcription, Nra functions as a positive regulator of pilus gene transcription in an M53 strain [20]. As already mentioned the hyaluronic acid capsule is an important virulence factor, required for resistance to complement-mediated phagocytic killing and thus is associated with enhanced virulence [1, 27, 38, 39]. Previous investigations LB-100 in vivo showed that acapsular mutant strains of GAS were impaired in pharyngeal colonization ability Alisertib molecular weight [38]. In contrary, highly encapsulated or mucoid strains

have been linked to acute rheumatic fever and severe invasive infections [5]. Various studies on regulation of capsule expression revealed that the regulatory protein BYL719 order Mga, shown to influence the expression of diverse GAS pathogenicity factors, affects the hyaluronic acid synthesis in GAS in a serotype- or strain- dependent mode. For instance, inactivation of Mga showed no effect on capsule production in an M6, M18 and M49 strain, but it resulted in decreased has operon transcription in a M1 strain [5]. However, as our results showed, the CovS- influenced depression of capsule formation in GAS is a uniform feature among divergent GAS serotypes tested. Moreover, our results confirm previous experiments from Bernish

and van de Rijn (1999) who showed that a non-polar inactivation of CovS in 3 unencapsulated strains rendered those strains highly mucoid [40]. The ability of S. pyogenes to adhere to its eukaryotic target cells is an essential factor both for causing disease and for persisting in its human host [16]. Therefore, the contribution of CovS to the adherence capacity of GAS in a serotype-dependent manner was additionally investigated. The results clearly showed that irrespective of their individual adherence abilities, the CovS inactivated mutants were inhibited

in their adherence to human keratinocytes in comparison with the corresponding parental wild type strains. Together with the fact that the hyaluronic acid masses of CovS mutant strains exceeded those detected for the Clomifene wild types, this could imply that the increased capsule material in the mutants could mask the exposure of important proteins involved in cell attachment and thus inhibit the process of attachment. Alternatively, CovS could act on important bacterial host cell adhesins either direct or via its influence on CovR. Furthermore, the effect of depression in adherence rate typical for the CovS- inactivated mutants was observed in all the serotype tested, which suggests that CovS influences the adherence of GAS in an unvarying mode. Of note, our data for the adherence capacity of CovS- inactivated GAS mutants contrasts the observation made for GBS, where a corresponding CovRS mutant exhibited increased adherence to epithelial cells [41, 42].