A number of bacterial cell processes are confined functional membrane microdomains (FMMs), structurally and functionally similar to lipid rafts of eukaryotic cells. How bacteria organize these intricate platforms and what their biological significance is remain important questions. Using the pathogen methicillin-resistant Staphylococcus aureus (MRSA), we show here that membrane-carotenoid interaction with the scaffold protein flotillin leads to FMM formation, which can be visualized using super-resolution array tomography. These membrane platforms accumulate multimeric protein complexes, for which flotillin facilitates efficient oligomerization. One of these proteins is PBP2a, responsible for penicillin resistance in MRSA. Flotillin mutants are defective in PBP2a oligomerization. Perturbation of FMM assembly using available drugs interferes with PBP2a oligomerization and disables MRSA penicillin resistance in vitro and in vivo, resulting in MRSA infections that are susceptible to penicillin treatment. Our study demonstrates that bacteria possess sophisticated cell organization programs and defines alternative therapies to fight multidrug-resistant pathogens using conventional antibiotics.

中文翻译：

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膜微区拆解抑制MRSA抗生素耐药性。

许多细菌细胞过程是局限性的功能膜微区（FMM），其结构和功能类似于真核细胞的脂筏。细菌如何组织这些复杂的平台及其生物学意义仍然是重要的问题。使用耐病原体耐甲氧西林的金黄色葡萄球菌（MRSA），我们在这里显示膜-类胡萝卜素与支架蛋白flotillin的相互作用导致FMM的形成，可以使用超分辨率阵列层析成像技术对其进行可视化。这些膜平台会积聚多聚体蛋白复合物，而Flottilin可促进有效的寡聚。这些蛋白之一是PBP2a，它负责MRSA中的青霉素抗性。Flotillin突变体在PBP2a寡聚化中存在缺陷。使用可用药物对FMM组件进行扰动会干扰PBP2a的寡聚，并在体外和体内使MRSA对青霉素的耐药性丧失，从而导致易受青霉素治疗的MRSA感染。我们的研究表明，细菌具有复杂的细胞组织程序，并定义了使用常规抗生素与多种耐药性病原体作斗争的替代疗法。