Journal
MARINE DRUGS
Volume 10, Issue 4, Pages 762-774Publisher
MDPI
DOI: 10.3390/md10040762
Keywords
epigenetics; fungus; mangrove; MRSA; malaria
Categories
Funding
- Medicines for Malaria Ventures [MMV08/0105]
- National Institute of Allergies and Infectious Diseases [1R01AI080626-01A2]
Ask authors/readers for more resources
Recent genomic studies have demonstrated that fungi can possess gene clusters encoding for the production of previously unobserved secondary metabolites. Activation of these attenuated or silenced genes to obtain either improved titers of known compounds or new ones altogether has been a subject of considerable interest. In our efforts to discover new chemotypes that are effective against infectious diseases, including malaria and methicillin-resistant Staphylococcus aureus (MRSA), we have isolated a strain of marine fungus, Leucostoma persoonii, that produces bioactive cytosporones. Epigenetic modifiers employed to activate secondary metabolite genes resulted in enhanced production of known cytosporones B (1, 360%), C (2, 580%) and E (3, 890%), as well as the production of the previously undescribed cytosporone R (4). Cytosporone E was the most bioactive, displaying an IC90 of 13 mu M toward Plasmodium falciparum, with A549 cytotoxicity IC90 of 437 mu M, representing a 90% inhibition therapeutic index (TI90 = IC90 A459/IC90 P. falciparum) of 33. In addition, cytosporone E was active against MRSA with a minimal inhibitory concentration (MIC) of 72 mu M and inhibition of MRSA biofilm at roughly half that value (minimum biofilm eradication counts, MBEC90, was found to be 39 mu M).
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available