An essential role for phoP in Mycobacterium tuberculosis virulence

An essential role for phoP in Mycobacterium tuberculosis virulence Two‐component regulatory proteins function in bacteria as sensory and adaptive factors in response to a wide range of environmental stimuli. Some two‐component systems, such as PhoP/PhoQ, control transcription of key virulence genes essential for survival in host cells in diverse intracellular bacterial pathogens, including Salmonella sp., Shigella sp. and Yersinia sp. In this study, we have disrupted the phoP gene from Mycobacterium tuberculosis, which codes for a putative transcription regulator factor of the two‐component system PhoP/PhoR. The phoP mutant strain exhibited impaired multiplication when cultured in mouse bone marrow‐derived macrophages. However, the mutation did not appear to affect survival of the organisms adversely inside macrophages. The mutant strain was also attenuated in vivo in a mouse infection model, with impaired growth observed in the lungs, livers and spleens. The results suggest that the phoP gene is required for intracellular growth of M. tuberculosis but is not essential for persistence of the bacilli. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Molecular Microbiology Wiley

An essential role for phoP in Mycobacterium tuberculosis virulence

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Publisher
Wiley
Copyright
Copyright © 2001 Wiley Subscription Services, Inc., A Wiley Company
ISSN
0950-382X
eISSN
1365-2958
DOI
10.1046/j.1365-2958.2001.02500.x
Publisher site
See Article on Publisher Site

Abstract

Two‐component regulatory proteins function in bacteria as sensory and adaptive factors in response to a wide range of environmental stimuli. Some two‐component systems, such as PhoP/PhoQ, control transcription of key virulence genes essential for survival in host cells in diverse intracellular bacterial pathogens, including Salmonella sp., Shigella sp. and Yersinia sp. In this study, we have disrupted the phoP gene from Mycobacterium tuberculosis, which codes for a putative transcription regulator factor of the two‐component system PhoP/PhoR. The phoP mutant strain exhibited impaired multiplication when cultured in mouse bone marrow‐derived macrophages. However, the mutation did not appear to affect survival of the organisms adversely inside macrophages. The mutant strain was also attenuated in vivo in a mouse infection model, with impaired growth observed in the lungs, livers and spleens. The results suggest that the phoP gene is required for intracellular growth of M. tuberculosis but is not essential for persistence of the bacilli.

Journal

Molecular MicrobiologyWiley

Published: Jul 1, 2001

References

  • Identification of a virulence gene cluster of Mycobacterium tuberculosis by signature‐tagged transposon mutagenesis
    Camacho, Camacho; Ensergueix, Ensergueix; Perez, Perez; Gicquel, Gicquel; Guilhot, Guilhot
  • Color selection with a hygromycin‐resistance‐based Escherichia coli– mycobacterial shuttle vector
    Howard, Howard; Gomez, Gomez; Ko, Ko; Bishai, Bishai
  • Generation and characterization of a PhoP homologue mutant of Neisseria meningitidis
    Johnson, Johnson; Newcombe, Newcombe; Thorne, Thorne; Borde, Borde; Eales‐Reynolds, Eales‐Reynolds; Gorringe, Gorringe
  • The regulatory protein PhoP controls susceptibility to the host inflammatory response in Shigella flexneri
    Moss, Moss; Fisher, Fisher; Vick, Vick; Groisman, Groisman; Zychlinsky, Zychlinsky
  • A. two‐component regulatory system playing a critical role in plant pathogens and endosymbionts is present in Brucella abortus and controls cell invasion and virulence
    Sola‐Landa, Sola‐Landa; Pizarro‐Cerda, Pizarro‐Cerda; Grillo, Grillo; Moreno, Moreno; Moriyon, Moriyon; Blasco, Blasco
  • Identification of novel intergenic repetitive units in a mycobacterial two‐component system operon
    Supply, Supply; Magdalena, Magdalena; Himpens, Himpens; Locht, Locht

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