Mycobacterial infection induces specific tRNA cleavage in the host cell – a response conserved from amoebae to macrophages

• Intracellular bacterial pathogens have to avoid the defenses of the host cell and create an environment in which they can replicate. This causes complex host-pathogen interactions, which are not fully understood. We have previously shown that infection by Mycobacterium marinum and Legionella pneumophila, respectively, induce large transcriptional rewiring in the model amoeba Dictyostelium discoideum. Although the major part of the responses was unique to each pathogen, both infections caused an up-regulation of RNA interference (RNAi) associated genes. Comparison to regulation in human macrophages after infection with Mycobacterium tuberculosis and L. pneumophila indicated that parts of the host-pathogen interaction, including the regulation of RNAi associated genes, are conserved.In this study, we investigate the effect on the small RNA population in D. discoideum when the amoeba was infected with M. marinum and L. pneumophila, respectively. Similar to the regulation of protein coding genes, we show that the two pathogens cause very different small RNA responses. M. marinum infection causes a dramatic up-regulation of specific tRNA halves, which was not observed in response to L. pneumophila or Klebsiella pneumonia. Furthermore, we show that this response is conserved in mammalian cells after infection by mycobacteria while L. pneumophila infection, as in D. discoideum, does not cause an increase in tRNA-halves.In summary, we demonstrate that infection by M. marinum induces major changes in the small RNA population of D. discoideum. This response is characterized by cleavage of specific host tRNAs, generating high levels of tRNA-halves, and is conserved in macrophages infected by M. tuberculosis.

Ämnesord

NATURVETENSKAP  -- Biologi -- Mikrobiologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Microbiology (hsv//eng)

Nyckelord

intracellular infection

Dictyostelium

microRNA

tRNA halves

Publikations- och innehållstyp

vet (ämneskategori)

ovr (ämneskategori)