| Autor: |
Bretl, Daniel J., He, Hongjun, Demetriadou, Crystalla, White, Mark J., Penoske, Renee M., Salzman, Nita H., Zahrt, Thomas C. |
| Zdroj: |
Infection and Immunity; June 2012, Vol. 80 Issue: 9 p3018-3033, 16p |
| Abstrakt: |
ABSTRACTMycobacterium tuberculosisremains a significant global pathogen, causing extensive morbidity and mortality worldwide. This bacterium persists within granulomatous lesions in a poorly characterized, nonreplicating state. The two-component signal transduction systems MprAB and DosRS-DosT (DevRS-Rv2027c) are responsive to conditions likely to be present within granulomatous lesions and mediate aspects of M. tuberculosispersistence in vitroand in vivo. Here, we describe a previously uncharacterized locus, Rv1813c-Rv1812c, that is coregulated by both MprA and DosR. We demonstrate that MprA and DosR bind to adjacent and overlapping sequences within the promoter region of Rv1813cand direct transcription from an initiation site located several hundred base pairs upstream of the Rv1813translation start site. We further show that Rv1813cand Rv1812care cotranscribed, and that the genomic organization of this operon is specific to M. tuberculosisand Mycobacterium bovis. Although Rv1813cis not required for survival of M. tuberculosisin vitro, including under conditions in which MprAB and DosRST signaling are activated, an M. tuberculosis?Rv1813cmutant is attenuated in the low-dose aerosol model of murine tuberculosis, where it exhibits a lower bacterial burden, delayed time to death, and decreased ability to stimulate proinflammatory cytokines interleukin-1ß (IL-1ß) and IL-12. Interestingly, overcomplementation of these phenotypes is observed in the M. tuberculosis?Rv1813cmutant expressing both Rv1813cand Rv1812c, but not Rv1813calone, in trans. Therefore, Rv1813c and Rv1812c may represent general stress-responsive elements that are necessary for aspects of M. tuberculosisvirulence and the host immune response to infection. |
| Databáze: |
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