Antifungal mechanism of SMAP-29 (1-18) isolated from sheep myeloid mRNA against Trichosporon beigelii

Biochem Biophys Res Commun. 2002 Jul 19;295(3):591-6. doi: 10.1016/s0006-291x(02)00717-9.

Abstract

The antifungal activity and mechanism of SMAP-29 (1-18) (SMAP-29), a cathelicidin-derived antimicrobial peptide deduced from N-terminal sequence of sheep myeloid mRNA, were investigated. SMAP-29 displayed a strong antifungal activity against various fungi. To understand the antifungal mechanism(s) of SMAP-29, we examined the interaction of SMAP-29 with the pathogenic fungus Trichosporon beigelii. Confocal microscopy showed that SMAP-29 was localized in the plasma membrane. The antifungal effects of SMAP-29 were further confirmed by using 1,6-diphenyl-1,3,5-hexatriene (DPH) as a plasma membrane probe. Flow cytometric analysis revealed that SMAP-29 acted in an energy-dependent manner. This interaction is also dependent on the ionic environment. Furthermore, SMAP-29 caused significant morphological changes when testing the membrane disrupting activity using liposomes (phosphatidylcholine/cholesterol; 10:1, w/w), as shown by scanning electron microscopy. The results suggest that SMAP-29 may exert its antifungal activity by disrupting the structure of cell membranes, via direct interaction with the lipid bilayers and irregularly disrupted fungal membranes in an energy- and salt-dependent manner.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antifungal Agents / pharmacology*
  • Blood Proteins / chemistry*
  • Blood Proteins / pharmacology*
  • Cathelicidins
  • Cell Membrane / metabolism
  • Cell Separation
  • Diphenylhexatriene / pharmacology
  • Dose-Response Relationship, Drug
  • Flow Cytometry
  • Fluorescein-5-isothiocyanate / pharmacology
  • Fluorescent Dyes / pharmacology
  • Ions
  • Lipid Bilayers / metabolism
  • Microscopy, Confocal
  • Microscopy, Electron, Scanning
  • Peptide Biosynthesis
  • Peptides / chemistry
  • RNA, Messenger / metabolism*
  • Saccharomyces cerevisiae / metabolism
  • Salts
  • Sheep
  • Sodium Azide / pharmacology
  • Trichosporon / metabolism*

Substances

  • Antifungal Agents
  • Blood Proteins
  • Cathelicidins
  • Fluorescent Dyes
  • Ions
  • Lipid Bilayers
  • Peptides
  • RNA, Messenger
  • SMAP29 protein, Ovis aries
  • Salts
  • Diphenylhexatriene
  • Sodium Azide
  • Fluorescein-5-isothiocyanate