Oral Presentation 20th Lancefield International Symposium on Streptococci and Streptococcal Diseases 2017

FasX is a virulence-regulating small regulatory RNA in the group A Streptococcus   (#79)

Jess Danger 1 , Paul Sumby 1
  1. University of Nevada Reno School of Medicine, Reno, NEVADA, United States
  Small regulatory RNAs (sRNAs) are a class of regulatory RNA molecule utilized by a majority of bacterial species to regulate gene expression; they are typically non-coding, and commonly function through post-transcriptional base-pairing mechanisms.  sRNAs are essential to the virulence of many pathogens, performing crucial tasks such as regulating stress responses and virulence factor expression.  Despite the importance of sRNAs in many pathogens, and the public health challenge posed by GAS, the contribution of sRNAs to GAS virulence has been studied only superficially.     We have characterized the 205 nucleotide sRNA FasX and identified that it both positively (the thrombolytic agent streptokinase) and negatively (the collagen-binding pilus, and fibronectin-binding PrtF1 and PrtF2 adhesins) regulates the expression of GAS virulence factors.  This regulation occurs post-transcriptionally through the direct binding of FasX to target mRNAs, modulating their stability and/or rate of translation.  The importance of FasX-mediated regulation to GAS virulence is highlighted by our findings that FasX reduces GAS adherence in a tissue culture-based model, and enhances disease severity in a bacteremia model of infection using humanized-plasminogen-expressing mice.   Our data are the first to mechanistically characterize sRNA activity in GAS, as well as the first to show these mechanisms contribute to the virulence of this pathogen, revealing the possibility of inhibiting FasX activity as a novel anti-infective strategy.  We propose that FasX functions as a molecular switch, governing the transition between colonization and dissemination during infection.