Fighting fungal AMR with soil bacteria
Screening soil bacteria to target Candida albicans and other fungal pathogens
What is the problem?
Tuberculosis, plague, transplant rejection, and cancer have one thing in common. They are all being treated with compounds produced by bacteria of the genus Streptomyces. These filamentous bacteria live in soil and sediments across the world and their genomes are enriched for biosynthetic pathways producing numerous compounds, including streptomycin for the treatment of tuberculosis and rapamycin, a powerful immunosuppressant. Although natural compounds produced by Streptomycetes have extensively been exploited in the clinical setting, their role in the treatment of fungal diseases is limited. Only one drug, Amphotericin B, produced by Streptomyces nodosus, has so far been shown to have antifungal activity. It is currently used as a last-line defense in the treatment of life-threatening fungal infections, such as systemic candidiasis and cryptococcal meningitis but application is burdened by severe side effects, such as nephrotoxicity.
Each year, the leading fungal pathogens of humans, Candida albicans and Cryptococcus neoformans cause invasive, life-threatening diseases in ~1,000,000 patients. With mortality rates up to 70%, this is unacceptably high. This already dire situation is further exacerbated by the emergence of the multi-drug resistant (MDR) species Candida auris. Even non-MDR fungal infections are difficult to treat as the available armamentarium of antifungal drugs is limited to four classes, some of which are only fungistatic rather than fungicidal and the identification of novel drug targets is challenging due to shared evolutionary ancestry.
What is the solution?
Dr Diezmann and her team screen soil bacteria for compounds active against Candida albicans, Cryptococcus neoformans and Candida auris. In collaboration with researchers from the University of Bath, the team hope to tackle fungal AMR by combining microbial screens with biochemical characterization of the compounds identified, and bacterial genome mining for secondary metabolite clusters. The end goal would be to develop an antifungal drug to reduce the mortality rate associated with fungal infections.
The team's research demonstrated that wild Streptomyces strains from Bavarian soil successfully killed fungi, and the researchers are currently expanding on this microbial screen.
- Dr Stephanie Diezmann (Cellular and Molecular Medicine)
- Professor Ruth Massey (Cellular and Molecular Medicine)
- Dr Susanne Gebhard (University of Bath)
- Dr Daniel Henk (University of Bath)