Surfactin and Capric Acid Affect the Posaconazole Susceptibility of Candida albicans Strains with Altered Sterols and Sphingolipids Biosynthesis

Int J Mol Sci. 2023 Dec 15;24(24):17499. doi: 10.3390/ijms242417499.

Abstract

Infections caused by Candida spp. pose a continuing challenge for modern medicine, due to widespread resistance to commonly used antifungal agents (e.g., azoles). Thus, there is considerable interest in discovering new, natural compounds that can be used in combination therapy with conventional antibiotics. Here, we investigate whether the natural compounds surfactin and capric acid, in combination with posaconazole, enhance the growth inhibition of C. albicans strains with alterations in sterols and the sphingolipids biosynthesis pathway. We demonstrate that combinations of posaconazole with surfactin or capric acid correspond with the decreased growth of C. albicans strains. Moreover, surfactin and capric acid can independently contribute to the reduced adhesion of C. albicans strains with altered ergosterol biosynthesis to abiotic surfaces (up to 90% reduction in adhesion). A microscopic study of the C. albicans plasma membrane revealed that combinations of those compounds do not correspond with the increased permeabilization of the plasma membrane when compared to cells treated with posaconazole alone. This suggests that the fungistatic effect of posaconazole in combination with surfactin or capric acid is related to the reduction in adhesion of C. albicans.

Keywords: Candida albicans; azole resistance; capric acid; posaconazole; surfactin; synergism.

MeSH terms

  • Antifungal Agents / metabolism
  • Antifungal Agents / pharmacology
  • Azoles / pharmacology
  • Candida albicans*
  • Microbial Sensitivity Tests
  • Phytosterols* / metabolism
  • Sphingolipids / metabolism
  • Sterols / metabolism
  • Sterols / pharmacology

Substances

  • posaconazole
  • decanoic acid
  • Sterols
  • Antifungal Agents
  • Azoles
  • Phytosterols
  • Sphingolipids