RIL-seq reveals extensive involvement of small RNAs in virulence and capsule regulation in hypervirulent Klebsiella pneumoniae
Kwok Jian Goh, Yael Altuvia, Liron Argaman, Yair Raz, Amir Bar, Hanah Margalit and Yunn-Hwen Gan
Hypervirulent Klebsiella pneumoniae (hvKp) are able to infect healthy individuals, in contrast to classical K. pneumoniae (Kp), which commonly cause nosocomial infections. The recent convergence of hypervirulence with carbapenem-resistance in Kp can potentially create “superbugs” that are very difficult to treat. Understanding virulence regulation of hvKp is thus critical. Accumulating evidence suggest that posttranscriptional regulation by small RNAs (sRNAs) play a role in virulence of hvKp, but it has hardly been studied. Here, we applied RIL-seq to a prototypical clinical isolate of hvKp, SGH10, to unravel the Hfq- dependent RNA-RNA interaction (RRI) network. Apparently, the RRI network is dominated by sRNAs, including predicted novel sRNAs, three of which we further validated experimentally. Constructing a stringent subnetwork composed of RRIs that involve at least one hvKp virulence-related gene, we identified the capsule locus as a hub target, where multiple sRNAs interact with capsule structural genes. We found that both capsule production and hypermucoviscosity are suppressed by sRNA OmrB binding to the capsule regulator KvrA. This agrees with current understanding of capsule as a major virulence and fitness factor, and reveals the intricate regulatory control of bacterial phenotypes by sRNAs, particularly of genes critical to bacterial physiology and virulence.
DOI: N/A