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Published on: August 31, 2015
New Insights Into The Melanin Structure Of Lomentospora prolificans
Livia C Liporagi-Lopes1,2, Christine Chrissian3, Arlind Kacirani3,4,5,6
1Molecular Microbiology and Immunology, Johns Hopkins School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
Abstract:
Lomentospora prolificans is a filamentous fungus with a global distribution, manifesting particularly higher prevalence in human-impacted environments. This organism is associated with a wide spectrum of human infections, especially in immunosuppressed individuals, for whom it causes severe and debilitating illnesses with high morbidity and mortality that are compounded by its pan-resistant profile with respect to antifungal drugs. Melanin is a ubiquitous pigment among fungi with a broad range of actions that include promoting fungal virulence. Although melanin is one of the most studied virulence factors in pathogenic fungi, relatively little is known about the chemistry of this pigment in L. prolificans. In the current study we characterized L. prolificans-associated melanin using chemical, biological, biophysical and structural techniques, also assessing the impact of inhibitors of distinct melanization pathways. Our results reveal that this pathogenic fungus makes multiple types of melanin pigments and suggests the possibility of a new type of melanin, which is synthesized together with a mixture of DHN-, DOPA- and pyomelanin types. These insights enhance our understanding of L. prolificans' virulence mechanisms, paving the way for potential therapeutic interventions.
Insights
This study reveals Lomentospora prolificans produces multiple melanin types, potentially including a novel form. Understanding these fungal pigments aids in developing new treatments for infections caused by this drug-resistant fungus.
Area of Science:
- Medical Mycology
- Fungal Biochemistry
- Pathogen Virulence Factors
Background:
- Lomentospora prolificans is a globally distributed fungus causing severe infections, particularly in immunocompromised individuals.
- This fungus exhibits pan-resistance to antifungal drugs, complicating treatment options.
- Melanin is a known fungal virulence factor, but its chemistry in L. prolificans remains poorly understood.
Purpose of the Study:
- To characterize the melanin produced by Lomentospora prolificans.
- To investigate the impact of melanization pathway inhibitors on pigment production.
- To elucidate the role of melanin in L. prolificans virulence.
Main Methods:
- Chemical, biological, and biophysical analyses of L. prolificans melanin.
- Structural characterization of fungal pigments.
- Assessment of melanization inhibitors.
Main Results:
- Lomentospora prolificans synthesizes multiple types of melanin pigments.
- Evidence suggests the presence of a novel melanin type alongside DHN-, DOPA-, and pyomelanin.
- Inhibitors targeting distinct melanization pathways were evaluated.
Conclusions:
- L. prolificans produces a complex mixture of melanins, potentially including a new type.
- These findings deepen the understanding of L. prolificans' virulence mechanisms.
- Characterizing L. prolificans melanin may lead to novel therapeutic strategies against this resilient pathogen.
