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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
Mutants of Mycobacterium tuberculosis lacking three of the five rpf-like genes are defective for growth in vivo and for resuscitation in vitro
Infection and Immunity, Volume 73, No. 5, Year 2005
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Description
Mycobacterium tuberculosis contains five genes, rpfA through rpfE, that bear significant homology to the resuscitation-promoting factor (rpf) gene of Micrococcus luteus, whose product is required to resuscitate the growth of dormant cultures of M. luteus and is essential for the growth of this organism. Previous studies have shown that deletion of any one of the five rpf-like genes did not affect the growth or survival of M. tuberculosis in vitro. In conjunction with the results of whole-genome expression profiling, this finding was indicative of their functional redundancy. In this study, we demonstrate that the single deletion mutants are phenotypically similar to wild-type M. tuberculosis H37Rv in vivo. The deletion of individual rpf-like genes had no discernible effect on the growth or long-term survival of M. tuberculosis in liquid culture, and the ability to resuscitate spontaneously from a nonculturable state in a most probable number assay was also unaffected for the three strains tested (the ΔrpfB, ΔrpfD, and ΔrpfE strains). In contrast, two multiple strains, KDT8 (ΔrpfA-mutation ΔrpfC ΔrpfB) and KDT9 (ΔrpfA ΔrpfC ΔrpfD), which lack three of the five rpf-like genes, were significantly yet differentially attenuated in a mouse infection model. These mutants were also unable to resuscitate spontaneously in vitro, demonstrating the importance of the Rpf-like proteins of M. tuberculosis in resuscitation from the nonculturable state. These results strongly suggest that the biological functions of the five rpf-like genes of M. tuberculosis are not wholly redundant and underscore the potential utility of these proteins as targets for therapeutic intervention. Copyright © 2005, American Society for Microbiology. All Rights Reserved.
Authors & Co-Authors
Downing, Katrina J.
South Africa, Johannesburg
University of the Witwatersrand
South Africa, Cape Town
University of Cape Town
Mischenko, Vladimir V.
Russian Federation, Moscow
Central Institute of Tuberculosis, Russian Academy of Medical Sciences
Shleeva, Margarita O.
Russian Federation, Moscow
Bach Institute of Biochemistry
Young, Danielle I.
United Kingdom, Aberystwyth
Aberystwyth University
Young, Michael
United Kingdom, Aberystwyth
Aberystwyth University
Kaprelyants, Arseny S.
Russian Federation, Moscow
Bach Institute of Biochemistry
Apt, Alexander S.
Russian Federation, Moscow
Central Institute of Tuberculosis, Russian Academy of Medical Sciences
Mizrahi, Valerie
South Africa, Johannesburg
University of the Witwatersrand
South Africa, Tygerberg
South African Medical Research Council
Statistics
Citations: 171
Authors: 8
Affiliations: 6
Identifiers
Doi:
10.1128/IAI.73.5.3038-3043.2005
ISSN:
00199567
Research Areas
Cancer
Genetics And Genomics
Study Design
Randomised Control Trial