Department of Chemistry, Indian Institute of Technology Bombay, Mumbai, 400076, India.
National Centre for Magnetic Resonance in Wuhan, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences, Wuhan, 430071, Hubei, China.
Chem Asian J. 2023 Dec 1;18(23):e202300697. doi: 10.1002/asia.202300697. Epub 2023 Oct 27.
The ability of Mycobacterium tuberculosis to remain dormant after primary infection represents the prime cause of new TB cases throughout the world. Hence, diagnosis and treatment of individuals hosting dormant mycobacterium is one of the crucial strategies to be adopted for the prevention of Tuberculosis. Among many strategies unleashed by the latent bacterium, one of them is scavenging host cholesterol for carbon source. Cholesterol modifies lipid membranes over many scales and here, its effect on mycobacterial membrane biophysics and the subsequent effect on partitioning of antibiotics into cholesterol- enriched mycobacterial membranes was investigated. Our research showed that cholesterol alters the phase state behavior of mycobacterial outer membrane lipids by enhancing the overall membrane order at the headgroup and acyl chain region and is integrated into both ordered and disordered domains/phases, with a preference for the latter. Exogenous cholesterol further alters the drug partitioning behavior of structurally different drugs, pointing to a larger clinical potential of using more hydrophobic medications to target dormant bacteria.
结核分枝杆菌在初次感染后保持休眠的能力是全世界新结核病病例的主要原因。因此，对休眠分枝杆菌宿主的诊断和治疗是预防结核病的关键策略之一。在潜伏细菌释放的许多策略中，其中之一是清除宿主胆固醇作为碳源。胆固醇在多个尺度上改变脂质膜，在这里，研究了它对分枝杆菌膜生物物理学的影响以及随后对富含胆固醇的分枝杆菌膜中抗生素分配的影响。我们的研究表明，胆固醇通过增强头部和酰基链区域的整体膜有序性来改变分枝杆菌外膜脂质的相态行为，并整合到有序和无序区域/相，优先整合到后者。外源性胆固醇进一步改变了结构不同的药物的药物分配行为，这表明使用更疏水的药物来靶向休眠细菌具有更大的临床潜力。
