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Wu, Chia-wei,Schmoller, Shelly K.,Shin, Sung Jae,Talaat, Adel M. American Society for Microbiology 2007 Journal of Bacteriology Vol.189 No.21
<B>ABSTRACT</B><P><I>Mycobacterium avium</I> subsp. <I>paratuberculosis</I> causes an enteric infection in cattle, with a great impact on the dairy industry in the United States and worldwide. Characterizing the gene expression profile of <I>M. avium</I> subsp. <I>paratuberculosis</I> exposed to different stress conditions, or shed in cow feces, could improve our understanding of the pathogenesis of <I>M. avium</I> subsp. <I>paratuberculosis</I>. In this report, the stress response of <I>M. avium</I> subsp. <I>paratuberculosis</I> on a genome-wide level (stressome) was defined for the first time using DNA microarrays. Expression data analysis revealed unique gene groups of <I>M. avium</I> subsp. <I>paratuberculosis</I> that were regulated under in vitro stressors while additional groups were regulated in the cow samples. Interestingly, acidic pH induced the regulation of a large number of genes (<I>n</I> = 597), suggesting the high sensitivity of <I>M. avium</I> subsp. <I>paratuberculosis</I> to acidic environments. Generally, responses to heat shock, acidity, and oxidative stress were similar in <I>M. avium</I> subsp. <I>paratuberculosis</I> and <I>Mycobacterium tuberculosis</I>, suggesting common pathways for mycobacterial defense against stressors. Several sigma factors (e.g., <I>sigH</I> and <I>sigE</I>) were differentially coregulated with a large number of genes depending on the type of each stressor. Subsequently, we analyzed the virulence of six <I>M. avium</I> subsp. <I>paratuberculosis</I> mutants with inactivation of differentially regulated genes using a murine model of paratuberculosis. Both bacterial and histopathological examinations indicated the attenuation of all gene mutants, especially those selected based on their expression in the cow samples (e.g., <I>lipN</I>). Overall, the employed approach profiled mycobacterial genetic networks triggered by variable stressors and identified a novel set of putative virulence genes. A similar approach could be applied to analyze other intracellular pathogens.</P>