Pangenomics Predicts Antifungal Siderotype of Pseudomonas aeruginosa 

Jacob Hudson (University of Kent, UK)

10:30 - 10:45 Wednesday 15 April Morning

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Abstract

Bacteria produce a broad spectrum of metabolites with key clinical and industrial applications. One such metabolite produced by Pseudomonas aeruginosa is the iron chelating siderophore pyoverdine (PVD), of which three common (PVDI-III) and one rare (PVD-IV) type are known. We have previously demonstrated that PVDI, produced by P. aeruginosa PAO1 and PA14, has antifungal efficacy against Mucorales fungi. These WHO priority pathogens are causative agents of mucormycosis, a disease with mortality rates reported as high as 96%. With only Amphotericin B and some Triazoles displaying limited efficacy further treatments are sorely needed. Identifying and characterising the lesser explored, and potentially unknown, PVD types would provide a range of new potential drug candidates. We identified the PVD biosynthesis region across all 464 complete P. aeruginosa genomes in the Pseudomonas Genome Database, and produced a pangenome graph of the region. This revealed three branches, differing in key PVD biosynthesis and import genes, likely corresponding to the three main PVD types. This allowed >98% of genomes to have a PVD type predicted. HMMs of type specific genes allowed concordant predictions of PVD type, which was validated with six strains producing a known to produce PVDI, II, or III molecule. Finally, we showed that each PVD type has antifungal efficacy against Mucorales, demonstrating the power of pangenomics to predict new metabolites of medical relevance and increasing the pool of potential mucormycosis treatments.

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