Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.ppat.1002264
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dc.titleEvaluating the sensitivity of mycobacterium tuberculosis to biotin deprivation using regulated gene expression
dc.contributor.authorPark S.
dc.contributor.authorKlotzsche M.
dc.contributor.authorWilson D.J.
dc.contributor.authorBoshoff H.I.
dc.contributor.authorEoh H.
dc.contributor.authorManjunatha U.
dc.contributor.authorBlumenthal A.
dc.contributor.authorRhee K.
dc.contributor.authorBarry C.E.
dc.contributor.authorAldrich C.C.
dc.contributor.authorEhrt S.
dc.contributor.authorSchnappinger D.
dc.date.accessioned2019-11-06T09:31:59Z
dc.date.available2019-11-06T09:31:59Z
dc.date.issued2011
dc.identifier.citationPark S., Klotzsche M., Wilson D.J., Boshoff H.I., Eoh H., Manjunatha U., Blumenthal A., Rhee K., Barry C.E., Aldrich C.C., Ehrt S., Schnappinger D. (2011). Evaluating the sensitivity of mycobacterium tuberculosis to biotin deprivation using regulated gene expression. PLoS Pathogens 7 (9) : e1002264. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.ppat.1002264
dc.identifier.issn15537366
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/161652
dc.description.abstractIn the search for new drug targets, we evaluated the biotin synthetic pathway of Mycobacterium tuberculosis (Mtb) and constructed an Mtb mutant lacking the biotin biosynthetic enzyme 7,8-diaminopelargonic acid synthase, BioA. In biotin-free synthetic media, ?bioA did not produce wild-type levels of biotinylated proteins, and therefore did not grow and lost viability. ?bioA was also unable to establish infection in mice. Conditionally-regulated knockdown strains of Mtb similarly exhibited impaired bacterial growth and viability in vitro and in mice, irrespective of the timing of transcriptional silencing. Biochemical studies further showed that BioA activity has to be reduced by approximately 99% to prevent growth. These studies thus establish that de novo biotin synthesis is essential for Mtb to establish and maintain a chronic infection in a murine model of TB. Moreover, these studies provide an experimental strategy to systematically rank the in vivo value of potential drug targets in Mtb and other pathogens. © 2011 This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
dc.sourceUnpaywall 20191101
dc.subject7,8 diaminopelargonic acid synthase
dc.subjectanhydrotetracycline
dc.subjectbiotin
dc.subjectbiotin derivative
dc.subjectdoxycycline
dc.subjectunclassified drug
dc.subjectaminotransferase
dc.subjectbacterial protein
dc.subjectBioA protein, bacteria
dc.subjectanimal experiment
dc.subjectanimal model
dc.subjectanimal tissue
dc.subjectarticle
dc.subjectbacterial growth
dc.subjectbacterial viability
dc.subjectbiotinylation
dc.subjectcontrolled study
dc.subjectenzyme activity
dc.subjectgene expression regulation
dc.subjectgene silencing
dc.subjectin vitro study
dc.subjectin vivo study
dc.subjectmouse
dc.subjectMycobacterium tuberculosis
dc.subjectnonhuman
dc.subjectprotein synthesis
dc.subjectquantitative analysis
dc.subjectsensitivity analysis
dc.subjectsignal transduction
dc.subjecttuberculosis
dc.subjectwild type
dc.subjectanimal
dc.subjectbiosynthesis
dc.subjectchronic disease
dc.subjectdisease model
dc.subjectdrug delivery system
dc.subjectenzymology
dc.subjectgenetics
dc.subjectmetabolism
dc.subjectmethodology
dc.subjectmutation
dc.subjecttuberculosis
dc.subjectBacteria (microorganisms)
dc.subjectMurinae
dc.subjectMus
dc.subjectMycobacterium tuberculosis
dc.subjectAnimals
dc.subjectBacterial Proteins
dc.subjectBiotin
dc.subjectChronic Disease
dc.subjectDisease Models, Animal
dc.subjectDrug Delivery Systems
dc.subjectMice
dc.subjectMutation
dc.subjectMycobacterium tuberculosis
dc.subjectTransaminases
dc.subjectTuberculosis
dc.typeArticle
dc.contributor.departmentDEPT OF MICROBIOLOGY & IMMUNOLOGY
dc.description.doi10.1371/journal.ppat.1002264
dc.description.sourcetitlePLoS Pathogens
dc.description.volume7
dc.description.issue9
dc.description.pagee1002264
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