The anti-Candida haemulonii activity and bioactive metabolites of Streptomyces anandii NC-SA6.

INTRODUCTION: The rapid advancement of multi-omics strategies has profoundly facilitated the in-depth exploration of microbial physiological characteristics, accelerated the discovery of novel bioactive secondary metabolites, and promoted the mechanistic elucidation of their biological functions. As a dominant genus within the phylum Actinomycetota, Streptomyces is widely recognized for its remarkable capacity to synthesize a diverse spectrum of clinically applicable antibiotics. Candida haemulonii, an emerging opportunistic fungal pathogen, has emerged as a typical multidrug-resistant species closely associated with outbreaks of nosocomial infections, posing a severe threat to clinical antifungal therapy.

METHODS: In this study, a novel strain designated as Streptomyces anandii NC-SA6 was isolated and systematically identified via gradient dilution method, multilocus sequence analysis (MLSA), coupled with comprehensive physiological and biochemical characterization assays. The optimal fermentation condition was optimized by controling a single variable method and measuring the diameter of the inhibition zone. The antimicrobial spectrum was tested against a panel of pathogenic strains, and the MIC value was measured by using broth microdilution. Finally, antifungal compounds were analyzed by combnining genome and metabolomic.

RESULTS: We identified a strain with a spectrum antimicrobial activity against human pathogenic Candida species and Gram-positive bacteria. The optimal fermentation conditions are 4-day fermentation broth in No. 6 medium, and the MIC values of S. anandii NC-SA6 fermentation broth for Candida auris BJCA001 and Candida haemulonii 190070, the MIC50 values were 36.8 mg/ml and 18.4 mg/ml, respectively. Whole-genome sequencing analysis revealed the presence of 20 biosynthetic gene clusters (BGCs) responsible for secondary metabolite biosynthesis. Untargeted metabolomic analysis identified a total of 1703 metabolites. Functional annotation demonstrated that 43.5% of these metabolites were characterized bioactive compounds, including antimicrobial agents, antifungal agents, antitumor inhibitors, and other pharmaceutical molecules; the remaining 56.5% were uncharacterized metabolites, indicating the existence of potential secondary metabolites.

DISCUSSION: Collectively, this integrated multi-omics study identified S. anandii NC-SA6 as a promising microbial resource for mining antifungal metabolites targeting multidrug-resistant C. haemulonii, highlighting its tremendous potential for the discovery and developmental research of novel antifungal agents.