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

Research output: Contribution to journalArticle

7 Scopus citations

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.

Original languageEnglish
Article number376
JournalMarine Drugs
Volume16
Issue number10
DOIs
StatePublished - 10 Oct 2018

    Fingerprint

Keywords

  • Endophytic fungi
  • Epigenetic modification
  • Infectious disease drug discovery
  • Mangroves
  • Screening

Cite this

Demers, D. H., Knestrick, M. A., Fleeman, R., Tawfik, R., Azhari, A., Souza, A., Vesely, B., Netherton, M., Gupta, R., Colon, B. L., Rice, C. A., Rodríguez-Pérez, M. A., Rohde, K. H., Kyle, D. E., Shaw, L. N., & Baker, B. J. (2018). Exploitation of mangrove endophytic fungi for infectious disease drug discovery. Marine Drugs, 16(10), [376]. https://doi.org/10.3390/md16100376