Structural insights into the interaction of antifungal peptides and ergosterol containing fungal membrane

Sk Abdul Mohid, Karishma Biswas, Tae Jun Won, Lakshmi S. Mallela, Arin Gucchait, Lena Butzke, Riddhiman Sarkar, Timothy Barkham, Bernd Reif, Enrico Leipold, Sanhita Roy, Anup K. Misra, Rajamani Lakshminarayanan, Dong Kuk Lee, Anirban Bhunia

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

The treatment of invasive drug-resistant and potentially life-threatening fungal infections is limited to few therapeutic options that are usually associated with severe side effects. The development of new effective antimycotics with a more tolerable side effect profile is therefore of utmost clinical importance. Here, we used a combination of complementary in vitro assays and structural analytical methods to analyze the interaction of the de novo antimicrobial peptide VG16KRKP with the sterol moieties of biological cell membranes. We demonstrate that VG16KRKP disturbs the structural integrity of fungal membranes both in vitro and in model membrane system containing ergosterol along with phosphatidylethanolamine lipid and exhibits broad-spectrum antifungal activity. As revealed by systematic structure-function analysis of mutated VG16KRKP analogs, a specific pattern of basic and hydrophobic amino acid side chains in the primary peptide sequence determines the selectivity of VG16KRKP for fungal specific membranes.

Original languageEnglish
Article number183996
JournalBiochimica et Biophysica Acta - Biomembranes
Volume1864
Issue number10
DOIs
StatePublished - 1 Oct 2022

Keywords

  • Antimicrobial peptide
  • Candida albicans
  • Nuclear magnetic resonance
  • Sterols

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