MAPS integrates regulation of actin-targeting effector SteC into the virulence control network of Salmonella small RNA PinT

• DOI: 10.1016/j.celrep.2021.108722
• Publication Date: 2021-02-03T14:51:54Z
• Authors: Sara Correia Santos; Thorsten Bischler; Alexander J. West...; Jörg Vogel
• Keywords: Salmonella typhimurium; 0301 basic medicine; Virulence; MS2 affinity purification and RNA-seq; host-pathogen interaction; post-transcriptional control; infection; noncoding RNA; 3. Good health; 03 medical and health sciences; Bacterial Proteins; Humans; RNA, Small Untranslated; ddc:570; PinT

A full understanding of the contribution of small RNAs (sRNAs) to bacterial virulence demands knowledge of their target suites under infection-relevant conditions. Here, we take an integrative approach to capturing targets of the Hfq-associated sRNA PinT, a known post-transcriptional timer of the two major virulence programs of Salmonella enterica. Using MS2 affinity purification and RNA sequencing (MAPS), we identify PinT ligands in bacteria under in vitro conditions mimicking specific stages of the infection cycle and in bacteria growing inside macrophages. This reveals PinT-mediated translational inhibition of the secreted effector kinase SteC, which had gone unnoticed in previous target searches. Using genetic, biochemical, and microscopic assays, we provide evidence for PinT-mediated repression of steC mRNA, eventually delaying actin rearrangements in infected host cells. Our findings support the role of PinT as a central post-transcriptional regulator in Salmonella virulence and illustrate the need for complementary methods to reveal the full target suites of sRNAs.