Abstract
ABSTRACTListeria monocytogenes is a bacterial pathogen causing severe foodborne infections in humans and animals. Listeria can enter into host cells and survive and multiply therein, due to an arsenal of virulence determinants encoded in different loci on the chromosome. Several key Listeria virulence genes are clustered in Listeria pathogenicity island 1. This important locus also contains orfX (lmo0206), a gene of unknown function. Here, we found that OrfX is a small, secreted protein whose expression is positively regulated by PrfA, the major transcriptional activator of Listeria virulence genes. We provide evidence that OrfX is a virulence factor that dampens the oxidative response of infected macrophages, which contributes to intracellular survival of bacteria. OrfX is targeted to the nucleus and interacts with the regulatory protein RybP. We show that in macrophages, the expression of OrfX decreases the level of RybP, which controls cellular infection. Collectively, these data reveal that Listeria targets RybP and evades macrophage oxidative stress for efficient infection. Altogether, OrfX is after LntA, the second virulence factor acting directly in the nucleus.
Highlights
Listeria monocytogenes is a bacterial pathogen causing severe foodborne infections in humans and animals
Since macrophages are important for the control of L. monocytogenes infection, we examined the role of OrfX in RAW 264.7 macrophages
Here, we report that OrfX is a small protein whose gene is activated by PrfA and secreted by L. monocytogenes that plays a critical role in virulence
Summary
Listeria monocytogenes is a bacterial pathogen causing severe foodborne infections in humans and animals. We found that OrfX is a small, secreted protein whose expression is positively regulated by PrfA, the major transcriptional activator of Listeria virulence genes. We report that the last gene of this locus encodes a small secreted nucleomodulin, OrfX, that is required for bacterial survival within macrophages and in the infected host. The genes encoding PrfA and the virulence factors necessary for intracellular survival are located on a single 9-kb locus of the L. monocytogenes chromosome, known as the virulence gene cluster or Listeria pathogenicity island 1 [4, 14]. The Ring YY1-binding protein RybP is a zinc finger protein that regulates gene expression at the transcriptional level by interacting with the Polycomb complex and acts as an adaptor to mediate protein-protein interactions [22] It is conserved in vertebrates and plays a vital role in embryonic development. Proapoptotic, and antioncogenic roles, RybP has recently been identified as a regulator of the innate immune response in Drosophila [30]
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