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Lipopeptide induces apoptosis in fungal cells by a mitochondria-dependent pathway

Gaofu Qi1, Fayin Zhu, Peng Du

  • 1State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, PR China.

Peptides
|August 18, 2010
PubMed

Insights

Bacillus amyloliquefaciens WH1 produces WH1fungin, a novel lipopeptide that inhibits fungal growth. WH1fungin induces fungal apoptosis through mitochondrial pathways and cell membrane damage, offering a new antifungal strategy.

Area of Science:

  • Microbiology
  • Biochemistry
  • Molecular Biology

Background:

  • Bacillus species are known for their antagonistic effects against fungi.
  • Surfactins are lipopeptides with diverse biological activities, including antimicrobial properties.
  • Understanding the precise mechanisms of Bacillus-mediated fungal inhibition is crucial for developing novel antifungal agents.

Purpose of the Study:

  • To investigate the antifungal mechanism of a novel surfactin, WH1fungin, produced by Bacillus amyloliquefaciens WH1.
  • To elucidate the molecular pathways involved in WH1fungin-induced fungal cell death.
  • To explore the potential of WH1fungin as a novel antifungal agent.

Main Methods:

  • Isolation and characterization of WH1fungin.
  • Assay of fungal growth inhibition by WH1fungin at different concentrations.
  • Detection of apoptotic markers (ROS, PS externalization, DNA breaks, caspase activity) in treated fungal cells.
  • Mitochondrial function analysis, including ATPase activity and cytochrome c release.
  • Confocal microscopy using FITC-labeled WH1fungin to determine its cellular localization.

Main Results:

  • WH1fungin inhibits fungal growth by inducing cell membrane pore formation at high concentrations and apoptosis at low concentrations.
  • WH1fungin treatment leads to the accumulation of reactive oxygen species (ROS), phosphatidylserine (PS) externalization, DNA strand breaks, and caspase-like activities.
  • WH1fungin binds to ATPase on the mitochondrial membrane, decreasing its activity and leading to cytochrome c release and caspase 9 activation.
  • Oligomycin, a mitochondrial apoptosis inhibitor, enhanced rather than inhibited WH1fungin-induced apoptosis.
  • Both intracellular (caspase 9) and extracellular (caspase 8) apoptotic pathways are implicated in WH1fungin's action.

Conclusions:

  • WH1fungin, a novel lipopeptide from Bacillus amyloliquefaciens WH1, exhibits potent antifungal activity through a dual mechanism involving cell membrane damage and apoptosis induction.
  • The lipopeptide targets fungal mitochondria, disrupting ATPase activity and triggering both intrinsic and extrinsic apoptotic pathways.
  • Apoptosis induction by lipopeptides may represent a common antifungal strategy employed by Bacillus species in natural environments.

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