Tuberculosis Research Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Drug Discovery Unit, College of Life Sciences, James Black Centre, University of Dundee, Dundee DD1 5EH, UK.
Science. 2020 Mar 6;367(6482):1147-1151. doi: 10.1126/science.aav5912.
has an unusual outer membrane that lacks canonical porin proteins for the transport of small solutes to the periplasm. We discovered that 3,3--di(methylsulfonyl)propionamide (3bMP1) inhibits the growth of , and resistance to this compound is conferred by mutation within a member of the proline-proline-glutamate (PPE) family, PPE51. Deletion of PPE51 rendered cells unable to replicate on propionamide, glucose, or glycerol. Growth was restored upon loss of the mycobacterial cell wall component phthiocerol dimycocerosate. Mutants in other proline-glutamate (PE)/PPE clusters, responsive to magnesium and phosphate, also showed a phthiocerol dimycocerosate-dependent growth compromise upon limitation of the corresponding substrate. Phthiocerol dimycocerosate determined the low permeability of the mycobacterial outer membrane, and the PE/PPE proteins apparently act as solute-specific channels.
它具有一种不寻常的外膜，缺乏用于将小溶质运输到周质空间的经典孔蛋白。我们发现 3,3--二（甲基磺酰基）丙酰胺（3bMP1）抑制 的生长，并且对该化合物的抗性是由脯氨酸-脯氨酸-谷氨酸（PPE）家族成员之一 PPE51 的突变赋予的。PPE51 的缺失使 细胞无法在丙酰胺、葡萄糖或甘油上复制。当失去分枝杆菌细胞壁成分 phthiocerol dimycocerosate 时，生长得到恢复。对镁和磷酸盐有反应的其他脯氨酸-谷氨酸（PE）/PPE 簇突变体在相应底物受到限制时，也表现出 phthiocerol dimycocerosate 依赖性生长受损。phthiocerol dimycocerosate 决定了分枝杆菌外膜的低通透性，而 PE/PPE 蛋白显然作为溶质特异性通道起作用。
