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Area of Science:

  • Microbiology
  • Bacterial Pathogenesis
  • Immunology

Background:

  • Pathogenic bacteria, including intracellular species like Salmonella enterica and Mycobacterium tuberculosis, utilize the MgtC virulence factor for intracellular survival.
  • MgtC is also present in pathogenic Pseudomonas species, but its role in extracellular pathogens like Pseudomonas aeruginosa was previously uninvestigated.

Purpose of the Study:

  • To elucidate the function of the MgtC virulence factor in the extracellular pathogen Pseudomonas aeruginosa.
  • To investigate the role of MgtC in bacterial virulence, host immune evasion, and adaptation to nutrient-limited environments.

Main Methods:

  • Utilized a Pseudomonas aeruginosa mgtC mutant in a systemic infection model using zebrafish embryos.
  • Conducted ex vivo experiments to assess bacterial survival and killing by macrophages.
  • Analyzed Pseudomonas aeruginosa mgtC gene expression within macrophages and investigated the role of phagosome acidification.

Main Results:

  • A P. aeruginosa mgtC mutant exhibited attenuated virulence in zebrafish embryos, with this phenotype being macrophage-dependent.
  • The mutant strain was more susceptible to macrophage killing, an effect reversed by inhibiting vacuolar proton ATPase, indicating MgtC's role in resisting phagosome acidification.
  • P. aeruginosa mgtC gene expression was induced within macrophages, requiring phagosome acidification for optimal expression, and MgtC was essential for growth in Mg2+-deprived media and preventing biofilm formation under Mg2+ limitation.

Conclusions:

  • Pseudomonas aeruginosa likely employs an intracellular stage during acute infections, with MgtC facilitating survival within macrophages via phagosome acidification.
  • MgtC contributes to bacterial adaptation in nutrient-poor environments and regulates biofilm formation, sharing functions with MgtC from intracellular pathogens.
  • MgtC is a potential anti-virulence target, as MgtC antagonism phenocopied the mutant's attenuated virulence.