NOVEL MARINE ANTIMICROBIAL LIPIDS

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Description (Adapted from Application): This proposal aims at the discovery of new marine lipids (either natural or synthetic) with potential applications as novel antimicrobial agents. The study of unusual and characteristic fatty acid profiles of marine microorganisms, some implicated in ciguatera food poisoning, is also contemplated in this research program. The long-range investigation is directed towards: 1) the discovery of new marine lipids (either natural or synthetic) with sufficient antimicrobial activity against pathogenic gram-positive bacteria (gram-negative bacteria will also occasionally be tested) so as to permit their utilization as antibacterial drugs or synergistically with known antibiotics, and 2) the synthesis of new synthetic fatty acid analogs, as well as alkylglycerol derivatives, with considerable antimicrobial activity against pathogenic antibiotic-resistant staphylococci and streptococci. In particular, the investigator proposes to expand the search for novel fatty acids to a series of tropical marine organisms (such as sponges rich in symbiotic cyanobacteria, marine bacteria, and toxic dinoflagellates) in search of previously unidentified fatty acids and/or novel structural motifs. The new fatty acids (and their analogs) will be synthesized, which will provide sufficient quantities for antimicrobial bioassays. In addition, alkylglycerol derivatives of the most promising antimicrobial fatty acids will also be synthesized since, in some cases, these derivatives tend to display stronger antimicrobial activity than the parent fatty acids. The new lipids will be primarily scrutinized for their antimicrobial activity against gram-positive bacteria (as suggested by preliminary results), such as pathogenic staphylococci and streptococci. They will put a special emphasis in the toxicity of these lipids against the cariogenic bacterium Streptococcus mutans, a primary cause of dental caries. The most active alkylglycerols and/or fatty acids will be further tested against known antibiotic-resistant bacteria, such as vancomycin resistant streptococci, chosen on the basis of their availability.