title: The small regulatory RNA FasX enhances group A Streptococcus virulence and inhibits pilus expression via serotype-specific targets.
abstract: 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.
authors.affiliation: Center for Molecular Medicine, Department of Microbiology & Immunology, University of Nevada, School of Medicine, Reno, Nevada, USA.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Danger
authors.forename: Tram N
authors.initials: TN
authors.lastname: Cao
authors.forename: Tran H
authors.initials: TH
authors.lastname: Cao
authors.forename: Poulomee
authors.initials: P
authors.lastname: Sarkar
authors.forename: Jeanette
authors.initials: J
authors.lastname: Treviño
authors.forename: Kathryn J
authors.initials: KJ
authors.lastname: Pflughoeft
authors.forename: Paul
authors.initials: P
authors.lastname: Sumby
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D010861:Fimbriae, Bacterial / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D051379:Mice; D012329:RNA, Bacterial / Q000235:genetics / Q000378:metabolism*; D065288:Serogroup; D013045:Species Specificity; D013290:Streptococcal Infections / Q000382:microbiology*; D013297:Streptococcus pyogenes / Q000145:classification / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D012329:RNA, Bacterial