Exploitation of Mangrove Endophytic Fungi for Infectious Disease Drug Discovery

Danielle  H. Demers; Matthew  A. Knestrick; Renee Fleeman; Rahmy Tawfik; Ala Azhari; Ashley Souza; Brian Vesely; Mandy Netherton; Rashmi Gupta; Beatrice  L. Colon; Christopher  A. Rice; Mario  A. Rodríguez-Pérez; Kyle  H. Rohde; Dennis  E. Kyle; Lindsey  N. Shaw; Bill  J. Baker

doi:10.3390/md16100376

Marine Drugs (Oct 2018)

Exploitation of Mangrove Endophytic Fungi for Infectious Disease Drug Discovery

Danielle H. Demers,
Matthew A. Knestrick,
Renee Fleeman,
Rahmy Tawfik,
Ala Azhari,
Ashley Souza,
Brian Vesely,
Mandy Netherton,
Rashmi Gupta,
Beatrice L. Colon,
Christopher A. Rice,
Mario A. Rodríguez-Pérez,
Kyle H. Rohde,
Dennis E. Kyle,
Lindsey N. Shaw,
Bill J. Baker

Affiliations

Danielle H. Demers: Department of Chemistry, University of South Florida, Tampa, FL 33620, USA
Matthew A. Knestrick: Department of Chemistry, University of South Florida, Tampa, FL 33620, USA
Renee Fleeman: Department of Cell Biology, Microbiology and Molecular Biology, University of South Florida, Tampa, FL 33620, USA
Rahmy Tawfik: Department of Cell Biology, Microbiology and Molecular Biology, University of South Florida, Tampa, FL 33620, USA
Ala Azhari: Department of Global Health, University of South Florida, Tampa, FL 33613, USA
Ashley Souza: Department of Global Health, University of South Florida, Tampa, FL 33613, USA
Brian Vesely: Department of Global Health, University of South Florida, Tampa, FL 33613, USA
Mandy Netherton: Division of Immunity and Pathogenesis, Burnett School of Biomedical Sciences, University of Central Florida, Orlando, FL 32827, USA
Rashmi Gupta: Division of Immunity and Pathogenesis, Burnett School of Biomedical Sciences, University of Central Florida, Orlando, FL 32827, USA
Beatrice L. Colon: Department of Molecular Medicine, University of South Florida, Tampa, FL 33613, USA
Christopher A. Rice: Department of Global Health, University of South Florida, Tampa, FL 33613, USA
Mario A. Rodríguez-Pérez: Instituto Politécnico Nacional, Centro de Biotecnología Genómica, Blvd. del Maestro esq. Elías Piña s/n. Reynosa 88710, Tamaulipas, Mexico
Kyle H. Rohde: Division of Immunity and Pathogenesis, Burnett School of Biomedical Sciences, University of Central Florida, Orlando, FL 32827, USA
Dennis E. Kyle: Department of Global Health, University of South Florida, Tampa, FL 33613, USA
Lindsey N. Shaw: Department of Cell Biology, Microbiology and Molecular Biology, University of South Florida, Tampa, FL 33620, USA
Bill J. Baker: Department of Chemistry, University of South Florida, Tampa, FL 33620, USA

DOI: https://doi.org/10.3390/md16100376
Journal volume & issue: Vol. 16, no. 10
p. 376

Abstract

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There is an acute need for new and effective agents to treat infectious diseases. We conducted a screening program to assess the potential of mangrove-derived endophytic fungi as a source of new antibiotics. Fungi cultured in the presence and absence of small molecule epigenetic modulators were screened against Mycobacterium tuberculosis and the ESKAPE panel of bacterial pathogens, as well as two eukaryotic infective agents, Leishmania donovani and Naegleria fowleri. By comparison of bioactivity data among treatments and targets, trends became evident, such as the result that more than 60% of active extracts were revealed to be selective to a single target. Validating the technique of using small molecules to dysregulate secondary metabolite production pathways, nearly half (44%) of those fungi producing active extracts only did so following histone deacetylase inhibitory (HDACi) or DNA methyltransferase inhibitory (DNMTi) treatment.

Published in Marine Drugs

ISSN: 1660-3397 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Biology (General)
Website: http://www.mdpi.com/journal/marinedrugs

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