Oxygen-dependent phenotypic variation in group A streptococcus.

The phenotypic heterogeneity of the human pathogen Streptococcus pyogenes [group A streptococcus (GAS)] is associated with bacterial virulence variation. During invasive GAS infection, mutations in the two-component regulatory system covR/covS leads to increases in hyaluronic acid capsule production, virulence genes expression, and lethality in the mouse infection model. Phenotypic variation of GAS is also found under in vitro culture conditions. However, whether a specific environmental factor is important for phenotypic variation is still unknown. GAS968 is an emm12-type clinical isolate that converts from mucoid to hypermucoid morphology under in vitro culture conditions. To clarify whether morphology variation can be triggered by specific environmental signals, or whether different morphology variants would be selected under specific environmental stresses, GAS968 was cultured under different conditions, and the changes in the number of mucoid and hypermucoid colonies in the total bacterial population were analyzed. The ratio of mucoid and hypermucoid colonies of GAS968 in the total bacterial population changes dramatically under aerobic and anaerobic conditions. The decrease in the number of hypermucoid colonies in the total bacterial population under aerobic conditions is not caused by growth repression, suggesting that the morphology conversion of GAS968 is inhibited by oxygen. Phenotypic heterogeneity has been shown to contribute to invasive GAS infection. Our results suggest that oxygen-dependent morphology variation in GAS968 may have important roles in bacterial pathogenesis.