Global Identification and Analysis of Small RNAs that Regulate Virulence in Pathogenic Yersinia Species
Wyndham W. Lathem, Northwestern University
Much like in eukaryotic cells, bacteria use small non-coding RNAs (sRNAs) to post-transcriptionally control gene expression. In the last two decades, it become clear that in conjunction with the small RNA chaperone Hfq, these molecules play an important role in regulating multiple aspects of cell physiology, including the virulence of bacterial pathogens. While the number of identified regulatory RNAs is on the order of hundreds, only a handful of bacterial genomes have been surveyed for a complete set of these regulators. Here, we describe the use of a deep sequencing approach to globally examine all of the sRNAs in both the human gastrointestinal pathogen Yersinia pseudotuberculosis and the closely related species Y. pestis, the causative agent of plague. We found that Y. pseudotuberculosis and Y. pestis each encodes a unique set of sRNAs whose expression are both thermally and temporally regulated. The majority of the identified RNAs are specific to Yersiniae and a subset contains single or multiple differences in nucleotide sequence that may be significant for interaction with mRNA targets. We also determined that multiple sRNAs are required for the full virulence of Y. pseudotuberculosis in animal models of infection, and that one specific RNA controls the synthesis of at least 8 Y. pseudotuberculosis proteins. Our work provides new insight into how sRNAs contribute to the pathogenesis of bacteria by regulating the expression of virulence determinants. Additionally, the genetic relatedness of Y. pestis and Y. pseudotuberculosis provides a unique framework in which to examine the subtle differences in regulatory RNAs that have accumulated between the species and may have contributed to the evolution of the highly virulent pathogen Y. pestis.