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

TitleMycobacteria counteract a TLR-mediated nitrosative defense mechanism in a zebrafish infection model.
Publication TypeJournal Article
Year of Publication2014
AuthorsElks, P.M., van der Vaart M., van Hensbergen V., Schutz E., Redd M.J., Murayama E., Spaink H.P., Meijer A.H.
JournalPLoS One
Volume9
Paginatione100928
Date Published2014
ISSN1932-6203
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.

DOI10.1371/journal.pone.0100928
Alternate JournalPLoS ONE
PubMed ID24967596
05/03/2015