The Small Protein YmoA Controls the Csr System and Adjusts Expression of Virulence-Relevant Traits of Yersinia pseudotuberculosis.

Katja Böhme,Anne-Sophie Stolle,Ann Kathrin Heroven,Stephanie Lobedann,Yuzhu Guo,Petra Dersch

doi:10.3389/fmicb.2021.706934

Katja Böhme, Anne-Sophie Stolle + Show 4 more

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https://doi.org/10.3389/fmicb.2021.706934

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Abstract

Virulence gene expression of Yersinia pseudotuberculosis changes during the different stages of infection and this is tightly controlled by environmental cues. In this study, we show that the small protein YmoA, a member of the Hha family, is part of this process. It controls temperature- and nutrient-dependent early and later stage virulence genes in an opposing manner and co-regulates bacterial stress responses and metabolic functions. Our analysis further revealed that YmoA exerts this function by modulating the global post-transcriptional regulatory Csr system. YmoA pre-dominantly enhances the stability of the regulatory RNA CsrC. This involves a stabilizing stem-loop structure within the 5′-region of CsrC. YmoA-mediated CsrC stabilization depends on H-NS, but not on the RNA chaperone Hfq. YmoA-promoted reprogramming of the Csr system has severe consequences for the cell: we found that a mutant deficient of ymoA is strongly reduced in its ability to enter host cells and to disseminate to the Peyer’s patches, mesenteric lymph nodes, liver and spleen in mice. We propose a model in which YmoA controls transition from the initial colonization phase in the intestine toward the host defense phase important for the long-term establishment of the infection in underlying tissues.

Highlights

Enteropathogenic yersiniae, Yersinia enterocolitica and Yersinia pseudotuberculosis are fecal-oral pathogens that can cause food-borne infections in animals and humans with symptoms ranging from self-limiting enteritis, mesenterial lymphadenitis to autoimmune responses (Bottone, 1997; Koornhof et al, 1999; Galindo et al, 2011)
In a previous study we showed that YmoA directly represses transcription of the regulator of lcrF, which is encoded on the Yersinia virulence plasmid and controls expression of the antiphagocytic T3SS machinery and effectors (Böhme et al, 2012)
In the context of a previous study addressing the influence of different early-stage virulence regulators (CsrA, cAMP-binding repressor protein (Crp), and RovA) on gene expression of Y. pseudotuberculosis YPIII (Bücker et al, 2014), we investigated the effect of YmoA on the Yersinia transcriptome

Summary

Introduction

Enteropathogenic yersiniae, Yersinia enterocolitica and Yersinia pseudotuberculosis are fecal-oral pathogens that can cause food-borne infections in animals and humans with symptoms ranging from self-limiting enteritis, mesenterial lymphadenitis to autoimmune responses (Bottone, 1997; Koornhof et al, 1999; Galindo et al, 2011) Both Yersinia species initiate infection after oral uptake in the gastrointestinal tract by tight adhesion to the mucosal surface of the intestine, which is followed by rapid internalization and translocation through M-cells of the intestinal epithelium (Pepe and Miller, 1993; Marra and Isberg, 1997; Koornhof et al, 1999). Expression of these virulence genes is activated by the AraC-type transcriptional regulator LcrF (VirF) (Lambert de Rouvroit et al, 1992; Hoe and Goguen, 1993; Böhme et al, 2012; Schwiesow et al, 2015) (Figure 1)

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