Investigator: Avelina Espinosa

Scientific Theme: Molecular Toxicology

Abstract: Entamoeba histolytica, the etiological agent of amebiasis, causes infections of 50 million people every year and 100 thousand fatalities worldwide. Despite the epidemiological importance of E. histolytica, there are currently no ideal methods to prevent infection in areas without appropriate sanitation. The development of a vaccine for amebiasis, although promising, has not been successful, thus metronidazole is the present drug of choice to treat amebiasis. Luminal amebicides (e.g. diloxanide furoate) are effective on intestinal lumen trophozoites but unable to reach tissue ameba; tissue amebicides (e.g. metronidazole, dehydroemetine, chloroquine, nitazoxanide) are effective on treating invasive amebiasis but incapable of controlling luminal trophozoites. Additionally, toxic side effects have been reported for metronidazole and its derivatives, the strongest rationale for the search/design of novel antiamebic compounds is a drug that manages both invasive and luminal amebiasis. Natural products have been used since early humans to relief pain, improve healing or overcome infections. More than 50 % of FDA-approved drugs originated from biological extracts or their derivatives. Two secondary metabolites isolated from marine actinomycetes were identified as effective anti-amoebic compounds, supporting this strategy to find novel drugs for managing amebiasis. The antibiotics echinomycin A and tirandamycin A inhibited the growth of E. histolytica at 30 to 60 µM concentrations, possibly by affecting its DNA replication. Phenolic-rich maple syrup extract has shown anticancer properties and, more recently, antibacterial activities against proteobacteria. This proposal aims at generating more effective anti-amebic agents by screening distinct types of natural products, i.e. marine actinomycete extracts and maple syrup derivatives. Aims: (1). Identify plant-derived products as safer, less toxic anti-amoebic alternatives and elucidate their mechanism of action. (2) Screen chemical extracts derived from fermentations of actinomycetes isolated from marine coastal sediments and elucidate their mechanism of action. An essential component is emphasizing the interdisciplinary biological and chemical perspective in training students interested in pursuing health related professions.

Human Health Relevance: This proposal will identify extracts from natural products that show novel anti-amebic properties, providing alternatives to manage amebiasis; expand basic chemical and biological knowledge on plant and marine microbial extracts; and provide an excellent training model for undergraduate students by incorporating an evolutionary perspective in the education of students interested in pursuing health related professions.