Control of Biofilms by Natural Products

描述（由申请人提供）：慢性细菌感染在美国是严重的医疗问题。在慢性细菌感染中，生物膜保护细菌免受抗生素和免疫反应机制的影响，从而增加症状复发率和对抗生素的耐药性。我们在这个STTR项目的第一阶段发现了四种新的化合物，它们可以防止生物膜的形成并破坏生物膜，我们希望在第二阶段发现更多的新化合物。我们建议使用第一阶段制定的战略，优先考虑已确定的其他活性样品。我们将阐明活性化合物的结构，并表征其作为生物膜抑制剂或抗菌剂的生物活性。我们还将继续发现更多的活性样品。这项工作将使我们能够将这些调节生物膜的化合物商业化，并进一步优化方法和策略，从而发现更新颖的调节生物膜形成的化合物，这些化合物是广泛应用所需的。在美国，微生物生物膜抑制剂的市场包含在85亿美元的抗生素市场中。生物膜参与了65%的人类细菌感染;因此，生物膜抑制剂可以占据40亿至60亿美元的抗生素市场。生物膜抑制剂将通过治疗许多慢性感染、减少导管和医疗器械相关感染以及治疗囊性纤维化患者而产生最大的医学影响。研究已经清楚地表明，生物膜在这些领域发挥着重要作用，代表了一个需求未得到满足的巨大市场。有效的生物膜抑制剂的潜在市场渗透是由生物膜引起医疗问题的案例数量所例证的。

DESCRIPTION (provided by applicant): Chronic bacterial infections are serious medical problems in the United States. In chronic bacterial infections, biofilms protect bacteria from antibiotics and immune response mechanisms, thus increasing the rates of reoccurring symptoms and resistance to antibiotics. We discovered four novel compounds in Phase I under this STTR project that prevent the formation and disrupt biofilms, and we expect to identify additional novel compounds in Phase II. We propose to use the strategies developed in Phase I to prioritize the other active samples that have been identified. We will elucidate the structures of the active compounds and characterize their biological activity as biofilm inhibitors or antibacterials. We will also continue the discovery process for additional active samples. This work will enable us to commercialize these compounds that regulate biofilms and to further optimize or methods and strategies by which to discover more novel compounds that regulate formation of biofilms that are needed for a wide range of applications. In the United States, the market for microbial biofilm inhibitors is contained within the $8.5 billion market for antibiotics. Biofilms are involved in 65% of human bacterial infections; accordingly, biofilm inhibitors could capture a $4 to $6-billion segment of the antibiotic market. Biofilm inhibitors will have the greatest medical impact by treating many chronic infections, reducing catheter- and medical device-related infections, and in treating cystic fibrosis patients. Research has clearly established that biofilms play a significant role in these areas, representing a large market whose needs are unmet. The potential market penetration for potent biofilm inhibitors is exemplified by the sheer number of cases in which biofilms cause medical problems.