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<p>Herein, one-pot synthesis of a nanosuspension of secondary metabolites (NSM) using antifungal secondary metabolites (SMs) derived from <i>Streptomyces chrestomyceticus</i> ADP4, stabilized with FDA-approved biodegradable polymer PEG-400, is reported. This is the first report on a microbe-derived nanosuspension displaying broad-spectrum antifungal activity against multiple <i>Candida</i> species. Transmission electron microscopy confirmed the formation of homogenously dispersed, spherical nanoparticles with an average diameter of 13.7 ± 4.6&#xa0;nm when in methanol and 13.9 ± 3.2&#xa0;nm in aqueous medium. Spectroscopic analysis via UV–Visible spectroscopy and Fourier Transform Infrared Spectroscopy (FTIR) demonstrated effective molecular interactions between SMs and PEG-400, facilitating enhanced dispersion and bioavailability of the NSM. Further, the enhanced efficacy and potency of NSM were demonstrated by a reduction in minimum inhibitory concentration (MIC) values when compared to the gross SMs, showing approximately 50% reduction against <i>Candida albicans</i>, 67% against <i>C. auris</i>, 75% against <i>C. tropicalis</i>, and 20% against <i>C. krusei</i>. Additionally, robust biofilm inhibition against <i>Candida albicans</i> ATCC 10,231, <i>Candida tropicalis</i> ATCC 750, <i>Candida krusei</i> ATCC 6258, and multi-drug resistant <i>Candida auris</i> CBS 12,372 was validated through scanning electron microscopy. Notably, plasma membrane fluorescence anisotropy studies revealed consistent fungal plasma membrane disruption with increasing NSM concentrations, highlighting mechanistic insight into its enhanced antifungal efficacy, followed by cell viability analysis. Collectively, these findings establish this NSM as a pioneering antifungal nanoformulation with potential applications in combating biofilm-associated fungal infections caused by WHO-listed priority <i>Candida</i> pathogens.</p>

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Actinobacterial metabolite-mediated nanosuspension: a novel approach to combat fungal infections

  • 期刊论文

  • 发表日期：

    2026年4月3日

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  • Shelly Singh,
  • Shilpa Sharma,
  • Ashok Kumar Dubey

摘要

Herein, one-pot synthesis of a nanosuspension of secondary metabolites (NSM) using antifungal secondary metabolites (SMs) derived from Streptomyces chrestomyceticus ADP4, stabilized with FDA-approved biodegradable polymer PEG-400, is reported. This is the first report on a microbe-derived nanosuspension displaying broad-spectrum antifungal activity against multiple Candida species. Transmission electron microscopy confirmed the formation of homogenously dispersed, spherical nanoparticles with an average diameter of 13.7 ± 4.6 nm when in methanol and 13.9 ± 3.2 nm in aqueous medium. Spectroscopic analysis via UV–Visible spectroscopy and Fourier Transform Infrared Spectroscopy (FTIR) demonstrated effective molecular interactions between SMs and PEG-400, facilitating enhanced dispersion and bioavailability of the NSM. Further, the enhanced efficacy and potency of NSM were demonstrated by a reduction in minimum inhibitory concentration (MIC) values when compared to the gross SMs, showing approximately 50% reduction against Candida albicans, 67% against C. auris, 75% against C. tropicalis, and 20% against C. krusei. Additionally, robust biofilm inhibition against Candida albicans ATCC 10,231, Candida tropicalis ATCC 750, Candida krusei ATCC 6258, and multi-drug resistant Candida auris CBS 12,372 was validated through scanning electron microscopy. Notably, plasma membrane fluorescence anisotropy studies revealed consistent fungal plasma membrane disruption with increasing NSM concentrations, highlighting mechanistic insight into its enhanced antifungal efficacy, followed by cell viability analysis. Collectively, these findings establish this NSM as a pioneering antifungal nanoformulation with potential applications in combating biofilm-associated fungal infections caused by WHO-listed priority Candida pathogens.