Department of Microbiology & Immunology, McGill Universitygrid.63984.30grid.14709.3b, Montréal, Québec, Canada.
Infectious Diseases and Immunity in Global Health Program, Research Institute of the McGill University Health Centregrid.63984.30, Montréal, Québec, Canada.
Microbiol Spectr. 2022 Dec 21;10(6):e0267222. doi: 10.1128/spectrum.02672-22. Epub 2022 Oct 31.
The prevalence of lung disease caused by Mycobacterium abscessus is increasing among patients with cystic fibrosis. M. abscessus is a multidrug resistant opportunistic pathogen that is notoriously difficult to treat due to a lack of efficacious therapeutic regimens. Currently, there are no standard regimens, and treatment guidelines are based empirically on drug susceptibility testing. Thus, novel antibiotics are required. Natural products represent a vast pool of biologically active compounds that have a history of being a good source of antibiotics. Here, we screened a library of 517 natural products purified from fermentations of various bacteria, fungi, and plants against M. abscessus ATCC 19977. Lysobactin and sorangicin A were active against the M. abscessus complex and drug resistant clinical isolates. These natural products merit further consideration to be included in the M. abscessus drug pipeline. The many thousands of people living with cystic fibrosis are at a greater risk of developing a chronic lung infection caused by Mycobacterium abscessus. Since M. abscessus is clinically resistant to most anti-TB drugs available, treatment options are limited to macrolides. Despite macrolide-based therapies, cure rates for M. abscessus lung infections are 50%. Using an in-house library of curated natural products, we identified lysobactin and sorangicin A as novel scaffolds for the future development of antimicrobials for patients with M. abscessus infections.
分枝杆菌属脓肿引起的肺部疾病在囊性纤维化患者中的发病率正在上升。脓肿分枝杆菌是一种多药耐药的机会性病原体，由于缺乏有效的治疗方案，治疗非常困难。目前尚无标准方案，治疗指南是根据药敏试验经验性制定的。因此，需要新型抗生素。天然产物是一类具有生物活性的化合物，它们是抗生素的重要来源，历史悠久。在这里，我们对来自各种细菌、真菌和植物发酵的 517 种天然产物文库进行了筛选，以检测其对脓肿分枝杆菌 ATCC 19977 的活性。溶菌素和山梨醇素 A 对脓肿分枝杆菌复合体和耐药临床分离株均具有活性。这些天然产物值得进一步考虑，将其纳入脓肿分枝杆菌药物研发管线。 数以千计的囊性纤维化患者面临着由脓肿分枝杆菌引起的慢性肺部感染的更大风险。由于脓肿分枝杆菌对大多数现有抗结核药物具有临床耐药性，因此治疗选择仅限于大环内酯类药物。尽管采用了基于大环内酯类的治疗方法，但脓肿分枝杆菌肺部感染的治愈率仍为 50%。我们使用内部 curated 天然产物文库，确定了溶菌素和山梨醇素 A 是未来开发针对脓肿分枝杆菌感染患者的抗菌药物的新型支架。
