Center for Discovery and Innovation, Hackensack Meridian Health , Nutley, New Jersey, USA.
Department of Medicinal Chemistry, College of Pharmacy, University of Minnesota , Minneapolis, Minnesota, USA.
Antimicrob Agents Chemother. 2023 Sep 19;67(9):e0038123. doi: 10.1128/aac.00381-23. Epub 2023 Jul 26.
Necrotic lesions and cavities filled with caseum are a hallmark of mycobacterial pulmonary disease. Bronchocavitary disease is associated with poor treatment outcomes. In caseum surrogate, entered an extended stationary phase showing tolerance to killing by most current antibiotics, suggesting that caseum persisters contribute to the poor performance of available treatments. Novel ADP-ribosylation-resistant rifabutin analogs exhibited bactericidal activity against these persisters at concentrations achievable by rifamycins in caseum.
干酪样坏死病变和充满干酪样物质的空洞是分枝杆菌肺病的一个标志。支气管空洞性疾病与治疗效果不佳有关。在干酪样物质替代物中，分枝杆菌进入延长的静止期，表现出对大多数现有抗生素的杀伤作用的耐受性，这表明干酪样物质的持续存在有助于现有治疗方法的疗效不佳。新型 ADP-ribosylation- resistant 利福布汀类似物在干酪样物质中可达到利福霉素浓度时对这些持续存在的分枝杆菌表现出杀菌活性。
