Exploitation of Mangrove Endophytic Fungi for Infectious Disease Drug Discovery

  title={Exploitation of Mangrove Endophytic Fungi for Infectious Disease Drug Discovery},
  author={D Demers and Matthew A. Knestrick and Renee M. Fleeman and Rahmy Tawfik and Ala Azhari and Ashley Souza and Brian A. Vesely and Mandy Netherton and Rashmi Gupta and Beatrice L. Colon and Christopher A. Rice and Mario A. Rodr{\'i}guez-P{\'e}rez and Kyle H. Rohde and Dennis E. Kyle and Lindsey N. Shaw and Bill J. Baker},
  journal={Marine Drugs},
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… 

Fungal Endophytes: A Promising Frontier for Discovery of Novel Bioactive Compounds

Endophytic fungi and their classification, rationale for selection and prioritization of host plants for fungal isolation and examples of strategies that have been adopted to induce the activation of cryptic biosynthetic gene clusters to enhance the biosynthesis potential of fungal endophytes are focused on.

How to Completely Squeeze a Fungus—Advanced Genome Mining Tools for Novel Bioactive Substances

An in-depth view of the chromatin-level regulation of BGCs and of the potential to use the CRISPR/Cas technology as an activation tool is provided.

Bioactive Compounds from Mangrove Endophytic Fungus and Their Uses for Microorganism Control

This review aims to highlight endophytic fungi isolated from mangrove plant species and the isolated bioactive compounds and their bioactivity against protozoa, bacteria and pathogenic viruses.

Natural products discovery and potential for new antibiotics.

Chromatographic editing enhances natural product discovery.

Differential Growth Rates and In Vitro Drug Susceptibility to Currently Used Drugs for Multiple Isolates of Naegleria fowleri

The data establish a needed baseline for drug susceptibility among clinical isolates and provide a segue for future combination therapy studies as well as research related to phenotypic or genetic differences that could shed light on mechanisms of action or predispositions to specific drugs.

Spongian Diterpenoids Derived from the Antarctic Sponge Dendrilla antarctica Are Potent Inhibitors of the Leishmania Parasite.

From the CH2Cl2 extract of the Antarctic sponge Dendrilla antarctica the authors found spongian diterpenes, including previously reported aplysulphurin, which displayed low micromolar activity against L. donovani with no discernible cytotoxicity against uninfected J774A.1 cells.



Screening Mangrove Endophytic Fungi for Antimalarial Natural Products

An accelerated discovery program based on small-scale cultivation for crude extract screening and a high-throughput malaria assay and criteria for advancing fractions to purification were developed, including the introduction of a selectivity index and by dereplication of known metabolites.

Miniaturized Cultivation of Microbiota for Antimalarial Drug Discovery

This microscale, high‐throughput screening project for antiplasmodial agents is discussed in the context of current natural product drug discovery efforts.

Epigenetic Tailoring for the Production of Anti-Infective Cytosporones from the Marine Fungus Leucostoma persoonii

A strain of marine fungus is isolated that produces bioactive cytosporones and was active against MRSA with a minimal inhibitory concentration (MIC) and inhibition of MRSA biofilm at roughly half that value (minimum biofilm eradication counts, MBEC90, was found to be 39 µM).

Methods for isolation of marine-derived endophytic fungi and their bioactive secondary products

This protocol gives a detailed description of methods useful for the isolation and cultivation of fungi associated with various marine organisms for the extraction, characterization and structure elucidation of biologically active secondary metabolites produced by these marine-derived endophytic fungi.

Bioactive natural compounds from the mangrove endophytic fungi.

The present report reviews the papers, which have appeared in the literature till now, concerning the isolation, structural elucidation, and biological activities of the secondary metabolites from mangrove endophytic fungi.

Small‐molecule elicitation of microbial secondary metabolites

Microbial natural products continue to be an unparalleled resource for pharmaceutical lead discovery, but the rediscovery rate is high. Bacterial and fungal sequencing studies indicate that the

LaeA, a Regulator of Secondary Metabolism in Aspergillus spp

A novel Aspergillus nuclear protein, LaeA, is presented here as a global regulator of secondary metabolism in this genus, and strains show little difference in spore production compared to the wild type, indicating that the primary role of laeA is to regulate metabolic gene clusters.

Selective Killing of Dormant Mycobacterium tuberculosis by Marine Natural Products

Four antimycobacterial compounds from marine organisms with novel activity profiles which appear to target M. tuberculosis pathways that are conditionally essential for dormancy survival are identified and characterized.

Regulation of fungal secondary metabolism

This Review describes the current understanding of the regulatory elements that modulate the transcription of genes involved in secondary metabolism and discusses how an improved knowledge of these regulatory elements will ultimately lead to a betterUnderstanding of the physiological and ecological functions of these important compounds.

Bis-Benzimidazole Hits against Naegleria fowleri Discovered with New High-Throughput Screens

The mono- and diamidino derivatives offer potential for lead optimization to develop new drugs to treat central nervous system infections with N. fowleri.