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 Gene Profiles


  RV1159A is profiled in 5 experiments

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The enduring hypoxic response of Mycobacterium tuberculosis.

Rustad TR, et al. (2008) PLoS ONE 3(1):e1502

Background A significant body of evidence accumulated over the last century suggests a link between hypoxic microenvironments within the infected host and the latent phase of tuberculosis. Studies to test this correlation have identified the M. tuberculosis initial hypoxic response, controlled by the two-component response regulator DosR. The initial hypoxic response is completely blocked in a dosR deletion mutant. ... Expand Methodology/Principal Findings We show here that a dosR deletion mutant enters bacteriostasis in response to in vitro hypoxia with only a relatively mild decrease in viability. In the murine infection model, the phenotype of the mutant was indistinguishable from that of the parent strain. These results suggested that additional genes may be essential for entry into and maintenance of bacteriostasis. Detailed microarray analysis of oxygen starved cultures revealed that DosR regulon induction is transient, with induction of nearly half the genes returning to baseline within 24 hours. In addition, a larger, sustained wave of gene expression follows the DosR-mediated initial hypoxic response. This Enduring Hypoxic Response (EHR) consists of 230 genes significantly induced at four and seven days of hypoxia but not at initial time points. These genes include a surprising number of transcriptional regulators that could control the program of bacteriostasis. We found that the EHR is independent of the DosR-mediated initial hypoxic response, as EHR expression is virtually unaltered in the dosR mutant. Conclusions/Significance Our results suggest a reassessment of the role of DosR and the initial hypoxic response in MTB physiology. Instead of a primary role in survival of hypoxia induced bacteriostasis, DosR may regulate a response that is largely optional in vitro and in mouse infections. Analysis of the EHR should help elucidate the key regulatory factors and enzymatic machinery exploited by M. tuberculosis for long-term bacteriostasis in the face of oxygen deprivation. Hide text

View RV1159A gene profile across 17 experiments

Download gene expression data in PCL format


The enduring hypoxic response of Mycobacterium tuberculosis.

Rustad TR, et al. (2008) PLoS ONE 3(1):e1502

Background A significant body of evidence accumulated over the last century suggests a link between hypoxic microenvironments within the infected host and the latent phase of tuberculosis. Studies to test this correlation have identified the M. tuberculosis initial hypoxic response, controlled by the two-component response regulator DosR. The initial hypoxic response is completely blocked in a dosR deletion mutant. ... Expand Methodology/Principal Findings We show here that a dosR deletion mutant enters bacteriostasis in response to in vitro hypoxia with only a relatively mild decrease in viability. In the murine infection model, the phenotype of the mutant was indistinguishable from that of the parent strain. These results suggested that additional genes may be essential for entry into and maintenance of bacteriostasis. Detailed microarray analysis of oxygen starved cultures revealed that DosR regulon induction is transient, with induction of nearly half the genes returning to baseline within 24 hours. In addition, a larger, sustained wave of gene expression follows the DosR-mediated initial hypoxic response. This Enduring Hypoxic Response (EHR) consists of 230 genes significantly induced at four and seven days of hypoxia but not at initial time points. These genes include a surprising number of transcriptional regulators that could control the program of bacteriostasis. We found that the EHR is independent of the DosR-mediated initial hypoxic response, as EHR expression is virtually unaltered in the dosR mutant. Conclusions/Significance Our results suggest a reassessment of the role of DosR and the initial hypoxic response in MTB physiology. Instead of a primary role in survival of hypoxia induced bacteriostasis, DosR may regulate a response that is largely optional in vitro and in mouse infections. Analysis of the EHR should help elucidate the key regulatory factors and enzymatic machinery exploited by M. tuberculosis for long-term bacteriostasis in the face of oxygen deprivation. Hide text

View RV1159A gene profile across 35 experiments

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Cell population heterogeneity in Mycobacterium tuberculosis H37Rv.

Andreu N and Gibert I (2008) Tuberculosis (Edinb) 88(6):553-9

The laboratory strain H37Rv represents one of the most commonly used strains in the study of Mycobacterium tuberculosis. Despite the apparent stability of the strain, the absence of a selective pressure for virulence factors could lead to the in vitro accumulation of attenuated mutants. To assess this hypothesis, we performed a systematic analysis of individual clones isolated from subcultured M. tuberculosis H37Rv ... Expand and from a non-subcultured frozen stock. First, we studied two virulence indicators: neutral red staining and content of phthiocerol dimycocerosates (PDIMs). We found that H37Rv formed a mixed population containing wild-type cells, as well as neutral red and PDIM mutants. Then, we compared the global gene expression of 3 isolated clones (which displayed various phenotypes) and the non-subcultured stock, by microarray analysis. This transcriptional profiling confirmed that a significant heterogeneity existed despite, and in addition to, the neutral red and PDIM phenotypes. These results strongly suggest that great caution must be taken in extrapolating data obtained with M. tuberculosis H37Rv grown in vitro, and it would be prudent to study several independent clones to obtain valid conclusions. For this purpose, the neutral red and PDIM phenotypes might be useful indicators of undesired heterogeneity. Hide text

View RV1159A gene profile across 21 experiments

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The transcriptional regulator Rv0485 modulates the expression of a pe and ppe gene pair and is required for Mycobacterium tuberculosis virulence.

Goldstone RM, et al. (2009) Infect Immun 77(10):4654-67

The pe and ppe genes are unique to mycobacteria and are widely speculated to play a role in tuberculosis pathogenesis. However, little is known about how expression of these genes is controlled. Elucidating the regulatory control of genes found exclusively in mycobacteria, such as the pe and ppe gene families, may be key to understanding the success of this pathogen. In this study, we used a transposon mutagenesis ... Expand approach to elucidate pe and ppe regulation. This resulted in the identification of Rv0485, a previously uncharacterized transcriptional regulator. Microarray and quantitative real-time PCR analysis confirmed that disruption of Rv0485 reduced the expression of the pe13 and ppe18 gene pair (Rv1195 and Rv1196), defined the Rv0485 regulon, and emphasized the lack of global regulation of pe and ppe genes. Hide text

View RV1159A gene profile across 6 experiments

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NAD+ auxotrophy is bacteriocidal for the tubercle bacilli.

Vilcheze C, et al. (2010) Mol Microbiol 76(2):365-77

Mycobacteria can synthesize NAD+ using either the de novo biosynthesis pathway or the salvage pathway. The deletion of the three genes involved specifically in the NAD+ de novo biosynthesis pathway in the human pathogen Mycobacterium tuberculosis had no effect on the growth of the strain in vivo. In contrast, the same deletion in the bovine pathogen Mycobacterium bovis resulted in a strain that could not grow in ... Expand vivo and could only grow in vitro with substantial nicotinamide supplmentation. This striking difference was attributed to the known defect in the nicotinamidase PncA of M. bovis, since introducing the M. tuberculosis pncA gene into the M. bovis strain defective for de novo NAD+ biosynthesis restored growth in vitro and in vivo. This study demonstrates that NAD+ starvation is a cidal event in mycobacteria and confirms that enzymes common to the de novo and salvage pathways may be good drug targets. We also propose that simultaneously targeting both the salvage and the de novo NAD+ biosynthesis pathways represents a potentially effective way to treat infection with tubercle bacilli. To characterize the lethality induced by nicotinamide starvation transcriptional profiling of the auxotrophs was performed. Triplicate 50 mL cultures of M. tuberculosis and M. bovis Delta nadABC mutants were grown in 7H9 OADC glycerol 0.05% tween broth in 500 mL roller bottles to an OD600nm= 0.1 in a roller incubator at 37oC. The cells were washed 1x in PBS and resuspended in 50 mL 7H9 OADC glycerol 0.05% tween broth with or without 20mg/L nicotinamide and returned to the incubator. After 7 days, cultures were harvested. Hide text

View RV1159A gene profile across 5 experiments

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