Reprogramming of from Virulent to Persistent Mode Revealed by Complex RNA-seq Analysis

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To establish infection and colonize within a host, infecting pathogens have to cope with a variety of destructive surroundings. The food-borne pathogen Y. pseudotuberculosis can cause persistent infection in mice. Upon infection, Y. pseudotuberculosis passes the anti-microbial gastrointestinal milieu and finally remains associated with lymphoid follicles in cecal tissue surrounded by polymorphonuclear leukocytes, indicating that the bacteria are exposed to multiple environmental cues. We performed complex RNA-seq of small cecal biopsies of infected mice to reveal Y. pseudotuberculosis gene expression in vivo. We found that Y. pseudotuberculosis underwent reprogramming from a virulent phenotype, expressing virulence genes during early infection, to an adapted phenotype capable of persisting in the harsh cecal environment. Persistence was characterized by a novel expression pattern with down-regulation of virulence genes and up-regulation of genes involved in anaerobiosis, chemotaxis, and protection against oxidative and acidic stress. Mutagenesis of selected genes revealed that the regulator rovA was critical for the establishment of infection, and that arcA, fnr, frdA, and wrbA play critical roles in maintaining infection for long periods of time. Our study shows the power of RNA deep sequencing, which can be used to reveal the in vivo expression patterns of small amounts of bacteria in complex intestinal environments.

Vyšlo v časopise: Reprogramming of from Virulent to Persistent Mode Revealed by Complex RNA-seq Analysis. PLoS Pathog 11(1): e32767. doi:10.1371/journal.ppat.1004600
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004600

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