In certain pathogenic fungi, melanin pigments contribute to virulence by protecting cells from external stresses such as oxidation, UV radiation, and fungicides. For instance, the opportunistic human pathogen Lomentospora prolificans is known to cause life-threatening infections in immunocompromised and cystic fibrosis patients. Although it has been established that L. prolificans produces dihydroxynaphthalene (DHN) melanin, evidence has begun to emerge suggesting that this organism also produces other types of melanins. To identify the different types of melanin pigments produced by this melanotic fungal organism, cells were grown in the presence of previously reported melanin biosynthesis pathway inhibitors; melanin samples were then isolated and examined using 13C solid-state NMR spectroscopy (ssNMR), EPR spectroscopy, surface Zeta potential, and elemental analysis. The initial results support the ability of L. prolificans to produce DHN melanin and also provide evidence to suggest that certain inhibitors promote the production of pyomelanin via the homogentisic acid (HGA) pathway. To determine whether the 3,4-dihydroxy-L-phenylalanine (L-DOPA) pathway inhibitor niacin is used as melanization substrate by L. prolificans, ssNMR spectroscopy was employed to examine isolated melanin pigments from cells grown in the presence of 13C-enriched niacin. The same analysis was carried out for isolated melanins generated from cells provided with natural abundance L-DOPA, a precursor in other melanotic fungi. The anticipated increase in spectral intensity was not observed from either sample suggesting that niacin and L-DOPA are likely to function as melanin-promoting signaling molecules rather than intermediates in a melanin biosynthesis pathway. Lastly, a previously reported HGA pathway inhibitor was found to diminish L. prolificans melanin production.

Aromatic ring structures upregulate fungal melanin biosynthesis: Spectroscopic characterization of L. prolificans cell walls

ACS Spring Meeting 2021

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