The resuscitation-promoting factors of Mycobacterium tuberculosis are required for virulence and resuscitation from dormancy but are collectively dispensable for growth in situ

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dc.contributor.author Kaprelyants, Arseny S.
dc.contributor.author Kana, B. D.
dc.contributor.author Young, Michael
dc.contributor.author Sung, N.
dc.contributor.author Gordhan, B. G.
dc.contributor.author Downing, Katrina J.
dc.contributor.author Machowski, E.
dc.contributor.author Tsenova, L.
dc.contributor.author Vostroktunova, G.
dc.contributor.author Kaplan, G.
dc.date.accessioned 2009-05-21T11:32:22Z
dc.date.available 2009-05-21T11:32:22Z
dc.date.issued 2008-02
dc.identifier.citation Kaprelyants , A S , Kana , B D , Young , M , Sung , N , Gordhan , B G , Downing , K J , Machowski , E , Tsenova , L , Vostroktunova , G & Kaplan , G 2008 , ' The resuscitation-promoting factors of Mycobacterium tuberculosis are required for virulence and resuscitation from dormancy but are collectively dispensable for growth in situ ' Molecular Microbiology , vol 67 , no. 3 , pp. 672-684 . en
dc.identifier.issn 1365-2958
dc.identifier.other PURE: 102553
dc.identifier.other dspace: 2160/2315
dc.identifier.uri http://hdl.handle.net/2160/2315
dc.identifier.uri http://www3.interscience.wiley.com/cgi-bin/fulltext/119408946/HTMLSTART en
dc.description Kana, B. D., Gordhan, B. G., Downing, K. J., Sung, N., Vostroktunova, G., Machowski, E. E., Tsenova, L., Young, M., Kaprelyants, A., Kaplan, G., Mizrahi, V. (2008). The resuscitation-promoting factors of Mycobacterium tuberculosis are required for virulence and resuscitation from dormancy but are collectively dispensable for growth in situ.  Molecular Microbiology, 67, (3), 672-684. Sponsorship: Wellcome Trust: Howard Hughes Medical Institute : National Research Foundation : South African Medical Research Council : Columbia University-Southern African Fogarty AIDS International Research and Training Program : GlaxoWellcome :Russian Academy of Sciences and the Russian Foundation for Basic Research. IMPF: 05.21 RONO: 00 en
dc.description.abstract Mycobacterium tuberculosis contains five resuscitation-promoting factor (Rpf)-like proteins, RpfA-E, that are implicated in resuscitation of this organism from dormancy via a mechanism involving hydrolysis of the peptidoglycan by Rpfs and partnering proteins. In this study, the rpfA-E genes were shown to be collectively dispensable for growth of M. tuberculosis in broth culture. The defect in resuscitation of multiple mutants from a 'non-culturable' state induced by starvation under anoxia was reversed by genetic complementation or addition of culture filtrate from wild-type organisms confirming that the phenotype was associated with rpf-like gene loss and that the 'non-culturable' cells of the mutant strains were viable. Other phenotypes uncovered by sequential deletion mutagenesis revealed a functional differentiation within this protein family. The quintuple mutant and its parent that retained only rpfD displayed delayed colony formation and hypersensitivity to detergent, effects not observed for mutants retaining only rpfE or rpfB. Furthermore, mutants retaining rpfD or rpfE were highly attenuated for growth in mice with the latter persisting better than the former in late-stage infection. In conjunction, these results are indicative of a hierarchy in terms of function and/or potency with the Rpf family, with RpfB and RpfE ranking above RpfD. en
dc.format.extent 13 en
dc.language.iso eng
dc.relation.ispartof Molecular Microbiology en
dc.title The resuscitation-promoting factors of Mycobacterium tuberculosis are required for virulence and resuscitation from dormancy but are collectively dispensable for growth in situ en
dc.type Text en
dc.type.publicationtype Article (Journal) en
dc.identifier.doi http://dx.doi.org/10.1111/j.1365-2958.2007.06078.x
dc.contributor.institution Institute of Biological, Environmental and Rural Sciences en
dc.description.status Peer reviewed en


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