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

Exploitation of Mangrove Endophytic Fungi for Infectious Disease Drug Discovery

Mar Drugs. 2018 Oct 10;16(10):376. doi: 10.3390/md16100376.

Authors

Danielle H Demers¹, Matthew A Knestrick², Renee Fleeman³, Rahmy Tawfik⁴, Ala Azhari⁵, Ashley Souza⁶, Brian Vesely⁷, Mandy Netherton⁸, Rashmi Gupta⁹, Beatrice L Colon¹⁰, Christopher A Rice¹¹, Mario A Rodríguez-Pérez¹², Kyle H Rohde¹³, Dennis E Kyle¹⁴, Lindsey N Shaw¹⁵, Bill J Baker¹⁶

Affiliations

¹ Department of Chemistry, University of South Florida, Tampa, FL 33620, USA. dhdemers@mail.usf.edu.
² Department of Chemistry, University of South Florida, Tampa, FL 33620, USA. m.a.knestrick@gmail.com.
³ Department of Cell Biology, Microbiology and Molecular Biology, University of South Florida, Tampa, FL 33620, USA. rfleeman@utexas.edu.
⁴ Department of Cell Biology, Microbiology and Molecular Biology, University of South Florida, Tampa, FL 33620, USA. rtawfik@mail.usf.edu.
⁵ Department of Global Health, University of South Florida, Tampa, FL 33613, USA. aazhari@kau.edu.sa.
⁶ Department of Global Health, University of South Florida, Tampa, FL 33613, USA. asouza@taskforce.org.
⁷ Department of Global Health, University of South Florida, Tampa, FL 33613, USA. bvesely@health.usf.edu.
⁸ Division of Immunity and Pathogenesis, Burnett School of Biomedical Sciences, University of Central Florida, Orlando, FL 32827, USA. Mandy.Netherton@ucf.edu.
⁹ Division of Immunity and Pathogenesis, Burnett School of Biomedical Sciences, University of Central Florida, Orlando, FL 32827, USA. Rashmi.Gupta@ucf.edu.
¹⁰ Department of Molecular Medicine, University of South Florida, Tampa, FL 33613, USA. Beatrice.Colon@uga.edu.
¹¹ Department of Global Health, University of South Florida, Tampa, FL 33613, USA. Christopher.Rice@uga.edu.
¹² Instituto Politécnico Nacional, Centro de Biotecnología Genómica, Blvd. del Maestro esq. Elías Piña s/n. Reynosa 88710, Tamaulipas, Mexico. mrodriguez@ipn.mx.
¹³ Division of Immunity and Pathogenesis, Burnett School of Biomedical Sciences, University of Central Florida, Orlando, FL 32827, USA. Kyle.Rohde@ucf.edu.
¹⁴ Department of Global Health, University of South Florida, Tampa, FL 33613, USA. DENNIS.KYLE@uga.edu.
¹⁵ Department of Cell Biology, Microbiology and Molecular Biology, University of South Florida, Tampa, FL 33620, USA. shaw@usf.edu.
¹⁶ Department of Chemistry, University of South Florida, Tampa, FL 33620, USA. bjbaker@usf.edu.

Abstract

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.

Keywords: endophytic fungi; epigenetic modification; infectious disease drug discovery; mangroves; screening.

MeSH terms

Animals
Anti-Bacterial Agents / pharmacology
Bacteria / drug effects
Cell Line
Communicable Diseases / drug therapy*
Drug Discovery / methods
Endophytes / metabolism*
Fungi / metabolism*
Histone Deacetylase Inhibitors / pharmacology
Methyltransferases / antagonists & inhibitors
Mice

Substances

Anti-Bacterial Agents
Histone Deacetylase Inhibitors
Methyltransferases

Abstract

MeSH terms

Substances

Grants and funding