NOVEL MARINE ANTIMICROBIAL LIPIDS

描述(改编自申请)：本提案旨在发现 新型海洋脂类(天然或合成)，具有潜在的应用 新型抗菌剂。特异型脂肪酸的研究进展 海洋微生物的概况，其中一些与雪卡毒素食物中毒有关， 在这项研究计划中也有考虑。长期的调查是 目标是：1)发现新的海洋脂类(天然或 合成的)对病原体具有足够的抗菌活性 革兰氏阳性菌(革兰氏阴性菌偶尔也会 测试)，以允许将其用作抗菌药物或 与已知抗生素的协同作用，以及2)新合成的 脂肪酸类似物，以及烷基甘油衍生物，具有相当大的 病原性耐药葡萄球菌的抗菌活性 和链球菌。 特别是，研究人员建议扩大对新脂肪的搜索 酸对一系列热带海洋生物(如富含 共生蓝藻、海洋细菌和有毒甲藻)正在寻找 以前未知的脂肪酸和/或新的结构基序。新的 脂肪酸(及其类似物)将被合成，这将提供 足够的数量进行抗菌素生物检测。此外，烷基甘油 最有希望的抗菌脂肪酸的衍生物也将是 合成，因为在某些情况下，这些衍生物往往表现出更强的 比母体脂肪酸具有更强的抗菌活性。新的脂类将是 主要针对它们对革兰氏阳性菌的抗菌活性进行审查 细菌(根据初步结果)，如致病菌 葡萄球菌和链球菌。他们将特别强调 这些脂类对致龋菌变形链球菌的毒性， 这是导致龋齿的主要原因。最活跃的烷基甘油和/或脂肪 酸将进一步测试已知的抗药性细菌，如 作为万古霉素耐药链球菌，根据它们的 可用性。

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.