Tags

Type your tag names separated by a space and hit enter

The Mycobacterium tuberculosis SigD sigma factor controls the expression of ribosome-associated gene products in stationary phase and is required for full virulence.
Cell Microbiol. 2005 Feb; 7(2):233-44.CM

Abstract

During infection Mycobacterium tuberculosis is exposed to several environmental conditions depending on the stage and severity of the disease. To survive, M. tuberculosis uses alternate sigma factors to regulate its gene expression in response to the changing host environment. In order to better understand the way in which stress response genes are regulated, the extracytoplasmic sigma factor gene sigD was deleted and subsequently complemented in the CDC1551 strain of M. tuberculosis. The DeltasigD mutant strain exhibited an in vitro growth rate in rich medium identical to that of both the sigD-complemented and wild-type CDC1551 strains. Additionally, no differences were observed in short-term intracellular growth between the mutant, complemented, and wild-type bacteria within the J774A.1 macrophage cell line. However, tumour necrosis factor (TNF)-alpha levels in macrophages infected with the DeltasigD mutant were decreased as compared to levels observed in macrophages infected with the wild-type bacteria. In time-to-death studies, C3H mice infected with the DeltasigD mutant exhibited a mortality delay compared to those infected with either the complemented or wild-type strains. Although mice infected with the DeltasigD mutant died at a reduced rate, the bacillary loads in the lungs and spleen of these mice were comparable to those seen in mice infected with either the complemented or wild-type strains. Microarray analysis of the DeltasigD mutant relative to wild type revealed that SigD directs the expression of a small set of ribosomal genes and adenosine triphosphate transporters whose expression is normally induced during stationary phase growth in vitro. Altered expression of a subset of these genes was confirmed by quantitative reverse transcription polymerase chain reaction analysis. Promoter-like elements resembling the consensus sequence AGAAAG-N16-20-CGTTAA were found upstream of 19 of the genes underexpressed in the DeltasigD mutant suggesting this may be the recognition sequence for the M. tuberculosis SigD-holoenzyme, EsigmaD. These data indicate that the M. tuberculosis SigD sigma factor governs the expression of a small set of ribosomal genes typically expressed in stationary phase during in vitro growth and that loss of sigD reduces macrophage TNF-alpha secretion as well as the lethality of M. tuberculosis infection in mice.

Authors+Show Affiliations

Center for Tuberculosis Research, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15659067

Citation

Calamita, Heather, et al. "The Mycobacterium Tuberculosis SigD Sigma Factor Controls the Expression of Ribosome-associated Gene Products in Stationary Phase and Is Required for Full Virulence." Cellular Microbiology, vol. 7, no. 2, 2005, pp. 233-44.
Calamita H, Ko C, Tyagi S, et al. The Mycobacterium tuberculosis SigD sigma factor controls the expression of ribosome-associated gene products in stationary phase and is required for full virulence. Cell Microbiol. 2005;7(2):233-44.
Calamita, H., Ko, C., Tyagi, S., Yoshimatsu, T., Morrison, N. E., & Bishai, W. R. (2005). The Mycobacterium tuberculosis SigD sigma factor controls the expression of ribosome-associated gene products in stationary phase and is required for full virulence. Cellular Microbiology, 7(2), 233-44.
Calamita H, et al. The Mycobacterium Tuberculosis SigD Sigma Factor Controls the Expression of Ribosome-associated Gene Products in Stationary Phase and Is Required for Full Virulence. Cell Microbiol. 2005;7(2):233-44. PubMed PMID: 15659067.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The Mycobacterium tuberculosis SigD sigma factor controls the expression of ribosome-associated gene products in stationary phase and is required for full virulence. AU - Calamita,Heather, AU - Ko,Chiew, AU - Tyagi,Sandeep, AU - Yoshimatsu,Tetsuyuki, AU - Morrison,Norman E, AU - Bishai,William R, PY - 2005/1/22/pubmed PY - 2005/9/9/medline PY - 2005/1/22/entrez SP - 233 EP - 44 JF - Cellular microbiology JO - Cell Microbiol VL - 7 IS - 2 N2 - During infection Mycobacterium tuberculosis is exposed to several environmental conditions depending on the stage and severity of the disease. To survive, M. tuberculosis uses alternate sigma factors to regulate its gene expression in response to the changing host environment. In order to better understand the way in which stress response genes are regulated, the extracytoplasmic sigma factor gene sigD was deleted and subsequently complemented in the CDC1551 strain of M. tuberculosis. The DeltasigD mutant strain exhibited an in vitro growth rate in rich medium identical to that of both the sigD-complemented and wild-type CDC1551 strains. Additionally, no differences were observed in short-term intracellular growth between the mutant, complemented, and wild-type bacteria within the J774A.1 macrophage cell line. However, tumour necrosis factor (TNF)-alpha levels in macrophages infected with the DeltasigD mutant were decreased as compared to levels observed in macrophages infected with the wild-type bacteria. In time-to-death studies, C3H mice infected with the DeltasigD mutant exhibited a mortality delay compared to those infected with either the complemented or wild-type strains. Although mice infected with the DeltasigD mutant died at a reduced rate, the bacillary loads in the lungs and spleen of these mice were comparable to those seen in mice infected with either the complemented or wild-type strains. Microarray analysis of the DeltasigD mutant relative to wild type revealed that SigD directs the expression of a small set of ribosomal genes and adenosine triphosphate transporters whose expression is normally induced during stationary phase growth in vitro. Altered expression of a subset of these genes was confirmed by quantitative reverse transcription polymerase chain reaction analysis. Promoter-like elements resembling the consensus sequence AGAAAG-N16-20-CGTTAA were found upstream of 19 of the genes underexpressed in the DeltasigD mutant suggesting this may be the recognition sequence for the M. tuberculosis SigD-holoenzyme, EsigmaD. These data indicate that the M. tuberculosis SigD sigma factor governs the expression of a small set of ribosomal genes typically expressed in stationary phase during in vitro growth and that loss of sigD reduces macrophage TNF-alpha secretion as well as the lethality of M. tuberculosis infection in mice. SN - 1462-5814 UR - https://www.unboundmedicine.com/medline/citation/15659067/The_Mycobacterium_tuberculosis_SigD_sigma_factor_controls_the_expression_of_ribosome_associated_gene_products_in_stationary_phase_and_is_required_for_full_virulence_ DB - PRIME DP - Unbound Medicine ER -