The small regulatory RNA FasX enhances group A Streptococcus virulence and inhibits pilus expression via serotype‐specific targets

Bacterial pathogens commonly show intra‐species variation in virulence factor expression and often this correlates with pathogenic potential. The group A Streptococcus (GAS) produces a small regulatory RNA (sRNA), FasX, which regulates the expression of pili and the thrombolytic agent streptokinase. As GAS serotypes are polymorphic regarding (a) FasX abundance, (b) the fibronectin, collagen, T‐antigen (FCT) region of the genome, which contains the pilus genes (nine different FCT‐types), and (c) the streptokinase‐encoding gene (ska) sequence (two different alleles), we sought to test whether FasX regulates pilus and streptokinase expression in a serotype‐specific manner. Parental, fasX mutant and complemented derivatives of serotype M1 (ska‐2, FCT‐2), M2 (ska‐1, FCT‐6), M6 (ska‐2, FCT‐1) and M28 (ska‐1, FCT‐4) isolates were compared. While FasX reduced pilus expression in each serotype, the molecular basis differed, as FasX bound, and inhibited the translation of, different FCT‐region mRNAs. FasX enhanced streptokinase expression in each serotype, although the degree of regulation varied. Finally, we established that the regulation afforded by FasX enhances GAS virulence, assessed by a model of bacteremia using human plasminogen‐expressing mice. Our data are the first to identify and characterize serotype‐specific regulation by an sRNA in GAS, and to show an sRNA directly contributes to GAS virulence.