Dataset Information

Mycobacteria counteract a TLR-mediated nitrosative defense mechanism in a zebrafish infection model.

ABSTRACT: Pulmonary tuberculosis (TB), caused by the intracellular bacterial pathogen Mycobacterium tuberculosis (Mtb), is a major world health problem. The production of reactive nitrogen species (RNS) is a potent cytostatic and cytotoxic defense mechanism against intracellular pathogens. Nevertheless, the protective role of RNS during Mtb infection remains controversial. Here we use an anti-nitrotyrosine antibody as a readout to study nitration output by the zebrafish host during early mycobacterial pathogenesis. We found that recognition of Mycobacterium marinum, a close relative of Mtb, was sufficient to induce a nitrosative defense mechanism in a manner dependent on MyD88, the central adaptor protein in Toll like receptor (TLR) mediated pathogen recognition. However, this host response was attenuated by mycobacteria via a virulence mechanism independent of the well-characterized RD1 virulence locus. Our results indicate a mechanism of pathogenic mycobacteria to circumvent host defense in vivo. Shifting the balance of host-pathogen interactions in favor of the host by targeting this virulence mechanism may help to alleviate the problem of infection with Mtb strains that are resistant to multiple drug treatments.

SUBMITTER: Elks PM

PROVIDER: S-EPMC4072692 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Mycobacteria counteract a TLR-mediated nitrosative defense mechanism in a zebrafish infection model.

Elks Philip M PM van der Vaart Michiel M van Hensbergen Vincent V Schutz Esther E Redd Michael J MJ Murayama Emi E Spaink Herman P HP Meijer Annemarie H AH

PloS one 20140626 6

Pulmonary tuberculosis (TB), caused by the intracellular bacterial pathogen Mycobacterium tuberculosis (Mtb), is a major world health problem. The production of reactive nitrogen species (RNS) is a potent cytostatic and cytotoxic defense mechanism against intracellular pathogens. Nevertheless, the protective role of RNS during Mtb infection remains controversial. Here we use an anti-nitrotyrosine antibody as a readout to study nitration output by the zebrafish host during early mycobacterial pat ...[more]

PMID: 24967596

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Project description:Plants can defend themselves against herbivores through activation of defensive pathways and attraction of third-trophic-level predators and parasites. Trophic cascades that mediate interactions in the phytobiome are part of a larger dynamic including the pathogens of the plant itself, which are known to greatly influence plant defenses. As such, we investigated the impact of a phloem-limited bacterial pathogen, Candidatus Liberibacter asiaticus (CLas), in cultivated citrus rootstock on a well-studied belowground tritrophic interaction involving the attraction of an entomopathogenic nematode (EPN), Steinernema diaprepesi, to their root-feeding insect hosts, Diaprepes abbreviatus larvae. Using belowground olfactometers, we show how CLas infection interferes with this belowground interaction by similarly inducing the release of a C12 terpene, pregeijerene, and disconnecting the association of the terpene with insect presence. D. abbreviatus larvae that were not feeding but in the presence of a CLas-infected plant were more likely to be infected by EPN than those near uninfected plants. Furthermore, nonfeeding larvae associated with CLas-infected plants were just as likely to be infected by EPN as those near noninfected plants with D. abbreviatus larval damage. Larvae of two weevil species, D. abbreviatus and Pachnaeus litus, were also more attracted to plants with infection than to uninfected plants. D. abbreviatus larvae were most active when exposed to pregeijerene at a concentration of 0.1 μg/μl. We attribute this attraction to CLas-infected plants to the same signal previously thought to be a herbivore-induced plant volatile specifically induced by root-feeding insects, pregeijerene, by assessing volatiles collected from the roots of infected plants and uninfected plants with and without feeding D. abbreviatus. Synthesis. Phytopathogens can influence the structuring of soil communities extending to the third trophic level. Field populations of EPN may be less effective at host-finding using pregeijerene as a cue in citrus grove agroecosystems with high presence of CLas infection.

Dataset Information

Mycobacteria counteract a TLR-mediated nitrosative defense mechanism in a zebrafish infection model.

Publications

Mycobacteria counteract a TLR-mediated nitrosative defense mechanism in a zebrafish infection model.

Similar Datasets

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