Development of New Drug Against Multidrug-Resistant Candidozyma (Candida) auris by Mining the Genome of Marine Bacteria Vibrio sp. IRMCESH58L

TL;DR

This study identifies a marine bacterium with potential antifungal properties against drug-resistant Candidozyma auris, offering a new therapeutic approach.

Contribution

The study discovers a novel marine bacterial strain with antifungal activity and identifies its biosynthetic gene clusters for drug development.

Findings

The IRMCESH58L strain showed strong and consistent antifungal activity against C. auris.

The genome of IRMCESH58L contains biosynthetic gene clusters for surfactin and other anti-C. auris compounds.

The strain exhibited no cytotoxicity against human cells, suggesting safety for further development.

Abstract

Background/Objectives: Candidozyma auris is the most frequent multidrug-resistant fungal infection in the Arabian Peninsula, with high mortality rates; therefore, new medications are in high demand. Microbes in marine habitats have genetically evolved to survive under a variety of adverse conditions, including severe temperatures, salinity, pH, and other stress factors, by generating various bioactive metabolites. These bioactive secondary metabolites have strong potential for use as antifungal agents. Due to the shortage of antifungal medications and the emergence of treatment resistance in C. auris, identifying new therapeutics from synthetic bacterial components or natural materials has become a necessity. Natural molecules have numerous advantages over synthetic substances, including structural variation and low toxicity. Few next-generation sequence-based investigations have been carried out on anti-Candidozyma auris bacterial species to identify potential therapeutic candidates. Therefore, the aim of this study is to identify biosynthetic gene clusters from marine bacteria using next-generation sequencing to discover novel drug compounds against multidrug-resistant C. auris. Methods: More than 68 isolates were collected from various marine environments using standard techniques. All isolates were tested against the multidrug-resistant C. auris. Scanning electron microscopy was utilized to investigate the cell membrane rupture caused by defused metabolites of the IRMCESH58L bacterium in C. auris. The Vibrio sp. IRMCESH58L genome was sequenced using long-read nanopore sequencing technology. Results: The bacterial strain IRMCESH58L, isolated from a fish liver sample, showed the highest and most constant activity against C. auris. An in vitro toxicity test found that IRMCESH58L had no cell cytotoxicity against HFF-1 cells. The assembled plasmid-free genome is 6,556,025 bp (48.93% G+C), with an N50 of 909243. Comparative analysis confirmed its relation to Vibrio alginolyticus. Conclusions: Whole-genome analysis of the native bacterial strain IRMCESH58L revealed various biosynthetic gene clusters, including those involved in surfactin’s biosynthesis of putative natural anti-C. auris chemicals, but no pathogenic protein-coding genes, emphasizing the importance of marine bacteria in the fight against C. auris. Following this in vivo study, therapeutic targets will later be selected for further pre-clinical studies.

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