Division of Infectious Diseases, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, RI 02903, USA.
Future Med Chem. 2018 Apr 1;10(7):779-794. doi: 10.4155/fmc-2017-0199. Epub 2018 Mar 23.
Chronic Staphylococcus aureus infections are complicated by frequent relapses not only from the development of drug resistance to conventional antibiotics, but also through the formation of persister bacterial cells. Bacterial persisters are in a transient, metabolically inactive state, making conventional antibiotics that target essential cellular growth processes ineffective, resulting in high clinical failure rates of antibiotic chemotherapy. The development of new antibiotics against persistent S. aureus is an urgent issue. Over the last decade, new strategies to identify S. aureus persister-active compounds have been proposed. This review summarizes the proposed targets, antipersister compounds and innovative methods that may augment conventional antibiotics against S. aureus persisters. The reviewed antipersister strategies can be summarized as two broad categories; directly targeting growth-independent targets and potentiating existing, ineffective antibiotics by aiding uptake or accessibility.
慢性金黄色葡萄球菌感染不仅因常规抗生素耐药性的发展而频繁复发，还因形成持留菌细胞而变得复杂。持留菌处于短暂的、代谢不活跃的状态，使针对关键细胞生长过程的常规抗生素无效，导致抗生素化疗的临床失败率很高。开发针对持留金黄色葡萄球菌的新抗生素是一个紧迫的问题。在过去的十年中，已经提出了新的策略来识别金黄色葡萄球菌持留活性化合物。这篇综述总结了针对金黄色葡萄球菌持留菌的可能增强常规抗生素的潜在靶点、抗持留化合物和创新方法。综述的抗持留策略可概括为两大类；直接针对非生长依赖性靶标和通过帮助摄取或可及性来增强现有无效抗生素。
