title: Overexpression of heat-shock proteins reduces survival of Mycobacterium tuberculosis in the chronic phase of infection.
abstract: Elevated expression of heat-shock proteins (HSPs) can benefit a microbial pathogen struggling to penetrate host defenses during infection, but at the same time might provide a crucial signal alerting the host immune system to its presence. To determine which of these effects predominate, we constructed a mutant strain of Mycobacterium tuberculosis that constitutively overexpresses Hsp70 proteins. Although the mutant was fully virulent in the initial stage of infection, it was significantly impaired in its ability to persist during the subsequent chronic phase. Induction of microbial genes encoding HSPs might provide a novel strategy to boost the immune response of individuals with latent tuberculosis infection.
authors.affiliation: Department of Infectious Diseases and Microbiology, Centre for Molecular Microbiology and Infection, Imperial College of Science Technology and Medicine, London, UK.
authors.forename: G R
authors.initials: GR
authors.lastname: Stewart
authors.forename: V A
authors.initials: VA
authors.lastname: Snewin
authors.forename: G
authors.initials: G
authors.lastname: Walzl
authors.forename: T
authors.initials: T
authors.lastname: Hussell
authors.forename: P
authors.initials: P
authors.lastname: Tormay
authors.forename: P
authors.initials: P
authors.lastname: O'Gaora
authors.forename: M
authors.initials: M
authors.lastname: Goyal
authors.forename: J
authors.initials: J
authors.lastname: Betts
authors.forename: I N
authors.initials: IN
authors.lastname: Brown
authors.forename: D B
authors.initials: DB
authors.lastname: Young
mesh_terms: D000818:Animals; D001426:Bacterial Proteins; D004591:Electrophoresis, Polyacrylamide Gel; D015870:Gene Expression; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000235:genetics; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008168:Lung / Q000382:microbiology / Q000473:pathology; D008264:Macrophages / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D009163:Mycobacterium bovis / Q000235:genetics / Q000502:physiology; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity / Q000502:physiology*; D012097:Repressor Proteins / Q000235:genetics; D013154:Spleen / Q000276:immunology / Q000378:metabolism; D013696:Temperature; D014376:Tuberculosis / Q000276:immunology / Q000382:microbiology* / Q000473:pathology
chemical_list: D001426:Bacterial Proteins; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C108444:HspR protein, bacteria; D012097:Repressor Proteins; D007371:Interferon-gamma