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Regulation of the Mycobacterium tuberculosis hypoxic response gene encoding alpha -crystallin.

TitleRegulation of the Mycobacterium tuberculosis hypoxic response gene encoding alpha -crystallin.
Publication TypeJournal Article
Year of Publication2001
AuthorsSherman DR, Voskuil M, Schnappinger D, Liao R, Harrell MI, Schoolnik GK
JournalProc Natl Acad Sci U S A
Volume98
Issue13
Pagination7534-9
Date Published2001 Jun 19
ISSN0027-8424
KeywordsAerobiosis, Anaerobiosis, Bacterial Proteins, Crystallins, Gene Expression Regulation, Bacterial, Kinetics, Mycobacterium tuberculosis, Time Factors
Abstract

Unlike many pathogens that are overtly toxic to their hosts, the primary virulence determinant of Mycobacterium tuberculosis appears to be its ability to persist for years or decades within humans in a clinically latent state. Since early in the 20th century latency has been linked to hypoxic conditions within the host, but the response of M. tuberculosis to a hypoxic signal remains poorly characterized. The M. tuberculosis alpha-crystallin (acr) gene is powerfully and rapidly induced at reduced oxygen tensions, providing us with a means to identify regulators of the hypoxic response. Using a whole genome microarray, we identified >100 genes whose expression is rapidly altered by defined hypoxic conditions. Numerous genes involved in biosynthesis and aerobic metabolism are repressed, whereas a high proportion of the induced genes have no known function. Among the induced genes is an apparent operon that includes the putative two-component response regulator pair Rv3133c/Rv3132c. When we interrupted expression of this operon by targeted disruption of the upstream gene Rv3134c, the hypoxic regulation of acr was eliminated. These results suggest a possible role for Rv3132c/3133c/3134c in mycobacterial latency.

DOI10.1073/pnas.121172498
Alternate JournalProc Natl Acad Sci U S A
PubMed ID11416222
PubMed Central IDPMC34703
Grant ListR01 AI044826 / AI / NIAID NIH HHS / United States
R01 AI047744 / AI / NIAID NIH HHS / United States
AI 44826 / AI / NIAID NIH HHS / United States

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