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Silencing of oxidative stress response in Mycobacterium tuberculosis: expression patterns of ahpC in virulent and avirulent strains and effect of ahpC inactivation.

ABSTRACT: Intracellular pathogens such as Mycobacterium tuberculosis are able to survive in the face of antimicrobial products generated by the host cell in response to infection. The product of the alkyl hydroperoxide reductase gene (ahpC) of M. tuberculosis is thought to be involved in protecting the organism against both oxidative and nitrosative stress encountered within the infected macrophage. Here we report that, contrary to expectations, ahpC expression in virulent strains of M. tuberculosis and Mycobacterium bovis grown in vitro is repressed, often below the level of detection, whereas expression in the avirulent vaccine strain M. bovis BCG is constitutively high. The repression of the ahpC gene of the virulent strains is independent of the naturally occurring lesions of central regulator oxyR. Using a green fluorescence protein vector (gfp)-ahpC reporter construct we present data showing that repression of ahpC of virulent M. tuberculosis also occurred during growth inside macrophages, whereas derepression in BCG was again seen under identical conditions. Inactivation of ahpC on the chromosome of M. tuberculosis by homologous recombination had no effect on its growth during acute infection in mice and did not affect in vitro sensitivity to H2O2. However, consistent with AhpC function in detoxifying organic peroxides, sensitivity to cumene hydroperoxide exposure was increased in the ahpC::Km(r) mutant strain. The preservation of a functional ahpC gene in M. tuberculosis in spite of its repression under normal growth conditions suggests that, while AhpC does not play a significant role in establishing infection, it is likely to be important under certain, as yet undefined conditions. This is supported by the observation that repression of ahpC expression in vitro was lifted under conditions of static growth.

SUBMITTER: Springer B

PROVIDER: S-EPMC98723 | biostudies-literature | 2001 Oct

REPOSITORIES: biostudies-literature

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Silencing of oxidative stress response in Mycobacterium tuberculosis: expression patterns of ahpC in virulent and avirulent strains and effect of ahpC inactivation.

Springer B B Master S S Sander P P Zahrt T T McFalone M M Song J J Papavinasasundaram K G KG Colston M J MJ Boettger E E Deretic V V

Infection and immunity 20011001 10

Intracellular pathogens such as Mycobacterium tuberculosis are able to survive in the face of antimicrobial products generated by the host cell in response to infection. The product of the alkyl hydroperoxide reductase gene (ahpC) of M. tuberculosis is thought to be involved in protecting the organism against both oxidative and nitrosative stress encountered within the infected macrophage. Here we report that, contrary to expectations, ahpC expression in virulent strains of M. tuberculosis and M ...[more]

PMID: 11553532

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Project description:Phosphorylation is a regulatory mechanism by which intracellular apicomplexan parasites control the process of invading and modifying host cells. However, the sporulated oocysts’ phosphoprotein repertoires between virulent and avirulent strains of Toxoplasma gondii and the underlying mechanisms contributing to virulence is still a mystery. A quantitative analysis of the sporulated oocysts’ phosphoproteome profile of T. gondii virulent and avirulent strains belonging to different genotypes was conducted to reveal phosphoprotein expression patterns that contribute to the virulence of a particular phenotype. Phosphopeptides from the sporulated oocysts of the virulent strain PYS (Chinese ToxoDB#9) and the avirulent strain type II (PRU strain) were enriched by titanium dioxide (TiO2) affinity chromatography and quantified using iBT technology. A total of 10,645 unique phosphopeptides, 8,181 nonredundant phosphorylation sites and 2,792 phosphoproteins were identified. The quantitative analysis identified 4,129 differentially expressed phosphopeptides (DEPs) between sporulated oocysts of the PYS strain and PRU strain (|log1.5 fold change| > 1 and P < 0.05), including 2,485 upregulated and 1,644 downregulated phosphopeptides. Motif analysis identified 24 motifs from the upregulated phosphorylated peptides including 22 serine motifs and two threonine motifs (TPE and TP), and 15 motifs from the downregulated phosphorylated peptides including 12 serine motifs and three threonine motifs (TP, RxxT and KxxT) in PYS strain when comparing PYS/PRU. Several kinases were consistent with motifs of overrepresented phosphopeptides, such as PKA, PKG, CKII, IKK, MAPK, EGFR, INSR, Jak, Syk, Src, Ab1. GO analysis, KEGG pathway analysis and STRING analysis revealed differentially expressed phosphoproteins (DEPs) exhibiting significant functional properties. Kinase associated network analysis showed that AGC kinase had the greatest connected peptides. Our findings reveal significant difference in phosphopeptides of sporulated oocysts between virulent and avirulent T. gondii strains, which provides solid foundation for further exploring the mechanisms contributing to the virulence of T. gondii.

Dataset Information

Silencing of oxidative stress response in Mycobacterium tuberculosis: expression patterns of ahpC in virulent and avirulent strains and effect of ahpC inactivation.

Publications

Silencing of oxidative stress response in Mycobacterium tuberculosis: expression patterns of ahpC in virulent and avirulent strains and effect of ahpC inactivation.

Similar Datasets

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