The non-proteic extrusive secondary metabolites in ciliated protists

The non-proteic extrusive secondary metabolites in ciliated protists F. Buonanno1, A. Anesi2, G. Guella2, E. Marcantoni3, S. Giorgi3, C. Ortenzi1 1Laboratory of Protistology and Biology Education, University of Macerata, 62100 Macerata, Italy 2Bioorganic Chemistry Laboratory, Department of Physics, University of Trento, 38050 Povo, Trento, Italy 3School of Sciences and Technologies, Section of Chemistry, University of Camerino, 62032 Camerino, Macerata, Italy Extrusomes are membrane-bound ejectable organelles widely distributed in protists. They are usually localized in the cell cortex and attached to the cell membrane, and they are able to discharge their contents to the outside of the cell in response to mechanical or chemical stimuli. Notably, cells that discharge their extrusomes remains intact and functional. The chemical nature of protists’ extrusive compounds characterized to date is extremely variable, including proteins, carbohydrates, lipids, and dozens of additional classes of secondary metabolites. However an increasing set of data are now available for particular group of protists, the ciliated protozoa. Many of non-proteic extrusive secondary metabolites in ciliates function for chemical offense or defense in prey-predator interactions against unicellular or/and multicellular organisms. It is worthy of note that at least some of these secondary metabolites have been demonstrated to show antibiotic, anti-cancer and pro-apoptotic properties in addition to their physiological functions. Among these compounds, euplotin C produced by the ciliate Euplotes crassus, and climacostol produced by Climacostomum virens, have been shown to activate programmed cell death by impairing mitochondrial membrane potential and inducing ROS generation in mammalian tumor cell lines. Interestingly, an antimicrobial activity against Gram-positive bacteria and fungal pathogens was also demonstrated for climacostol. Overall, in addition to the understanding of their physiological and ecological functions, the study of non-proteic secondary metabolites of ciliated protozoa may set the basis for the development of a novel series of antitumor and antimicrobial agents.