title: A family of autocrine growth factors in Mycobacterium tuberculosis.
abstract: Mycobacterium tuberculosis and its close relative, Mycobacterium bovis (BCG) contain five genes whose predicted products resemble Rpf from Micrococcus luteus. Rpf is a secreted growth factor, active at picomolar concentrations, which is required for the growth of vegetative cells in minimal media at very low inoculum densities, as well as the resuscitation of dormant cells. We show here that the five cognate proteins from M. tuberculosis have very similar characteristics and properties to those of Rpf. They too stimulate bacterial growth at picomolar (and in some cases, subpicomolar) concentrations. Several lines of evidence indicate that they exert their activity from an extra-cytoplasmic location, suggesting that they are also involved in intercellular signalling. The five M. tuberculosis proteins show cross-species activity against M. luteus, Mycobacterium smegmatis and M. bovis (BCG). Actively growing cells of M. bovis (BCG) do not respond to these proteins, whereas bacteria exposed to a prolonged stationary phase do. Affinity-purified antibodies inhibit bacterial growth in vitro, suggesting that sequestration of these proteins at the cell surface might provide a means to limit or even prevent bacterial multiplication in vivo. The Rpf family of bacterial growth factors may therefore provide novel opportunities for preventing and controlling mycobacterial infections.
authors.affiliation: Institute of Biological Sciences, University of Wales, Aberystwyth, Ceredigion SY23 3 DD, UK.
authors.forename: Galina V
authors.initials: GV
authors.lastname: Mukamolova
authors.forename: Obolbek A
authors.initials: OA
authors.lastname: Turapov
authors.forename: Danielle I
authors.initials: DI
authors.lastname: Young
authors.forename: Arseny S
authors.initials: AS
authors.lastname: Kaprelyants
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Kell
authors.forename: Michael
authors.initials: M
authors.lastname: Young
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D015169:Colony Count, Microbial; D003470:Culture Media; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D006133:Growth Substances / Q000235:genetics* / Q000378:metabolism; D016982:Micrococcus luteus / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D005810:Multigene Family; D009163:Mycobacterium bovis / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D001426:Bacterial Proteins; D003470:Culture Media; D016207:Cytokines; D006133:Growth Substances; D011994:Recombinant Proteins; C113704:resuscitation-promoting factor, bacteria