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A bacterial virulence protein promotes pathogenicity by inhibiting the bacterium's own F1Fo ATP synthase

Eun-Jin Lee1, Mauricio H Pontes, Eduardo A Groisman

  • 1Department of Microbial Pathogenesis, Boyer Center for Molecular Medicine, Yale School of Medicine, 295 Congress Avenue, New Haven, CT 06536-0812, USA.

Cell
|July 6, 2013
PubMed

Insights

The virulence protein MgtC helps pathogens like Salmonella survive inside host cells by disrupting their energy production. MgtC interferes with the F1Fo ATP synthase, impacting bacterial ATP levels and pathogenicity.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Pathogenesis

Background:

  • Intracellular pathogens Salmonella enterica and Mycobacterium tuberculosis rely on the MgtC virulence protein for survival within macrophages.
  • MgtC is crucial for causing lethal infections in mouse models.
  • Unlike secreted factors targeting host machinery, MgtC acts intracellularly on bacterial components.

Purpose of the Study:

  • To elucidate the molecular mechanism by which MgtC contributes to pathogen virulence.
  • To investigate the interaction of MgtC with Salmonella's energy-producing F1Fo ATP synthase.
  • To determine the role of MgtC in regulating intracellular ATP levels and pathogenicity.

Main Methods:

  • Biochemical assays to study the interaction between MgtC and the F1Fo ATP synthase.
  • Analysis of proton translocation and ATP synthesis in bacterial vesicles.
  • Construction and characterization of mgtC null mutants and MgtC variants.
  • Assessment of bacterial ATP levels, cytoplasmic pH, and pathogenicity in vivo.

Main Results:

  • MgtC directly interacts with the 'a' subunit of the F1Fo ATP synthase.
  • This interaction inhibits ATP-driven proton translocation and NADH-driven ATP synthesis.
  • mgtC null mutants exhibit elevated ATP levels and an acidic cytoplasm.
  • Overexpression of MgtC leads to decreased ATP levels.
  • A specific MgtC mutation preventing F1Fo ATP synthase binding abolishes ATP level control and reduces pathogenicity.

Conclusions:

  • MgtC is a unique virulence factor that enhances pathogenicity by inhibiting the bacterial F1Fo ATP synthase.
  • This mechanism allows pathogens to manipulate their intracellular environment and energy metabolism for survival.
  • Interference with the F1Fo ATP synthase represents a novel strategy for virulence employed by MgtC.

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