Unknown,Transcriptomics,Genomics,Proteomics

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Mycobacterium tuberculosis CDC1551 WT/sigI mutant

ABSTRACT: Transcription profile of WT compare to sigma factor sigI deletion mutant at OD1 and OD2. This microarray is simple comparison of wild type strain of M. tuberculosis CDC1551 and its sigma factor gene deletion mutant (sigI) at OD1 and OD2, respectively.

ORGANISM(S): Mycobacterium tuberculosis CDC1551

SUBMITTER: JongHee Lee

PROVIDER: E-GEOD-35231 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description: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. 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. Keywords: time-course Each hypoxic timecourse compared to the matching log phase sample. Each time point/strain represented by a minimum of three replicates.

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Mycobacterium tuberculosis CDC1551 WT/sigI mutant

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