Menon Anjana P, Lee Tzong-Hsien, Aguilar Marie-Isabel, Kapoor Shobhna
Department of Chemistry, Indian Institute of Technology Bombay Mumbai 400076 India
IITB-Monash Research Academy, Indian Institute of Technology Bombay Mumbai 400076 India
Chem Sci. 2024 Oct 29;15(45):19084-93. doi: 10.1039/d4sc06618a.
Current treatments for tuberculosis primarily target () infections, often neglecting the emerging issue of latent tuberculosis infection (LTBI) which are characterized by reduced susceptibility to antibiotics. The bacterium undergoes multiple adaptations during dormancy within host granulomas, leading to the development of antibiotic-tolerant strains. The mycobacterial membrane plays a crucial role in drug permeability, and this study aims to characterize membrane lipid deviations during dormancy through extensive lipidomic analysis of bacteria cultivated in distinct media and growth stages. The results revealed that specific lipids localize in different regions of the membrane envelope, allowing the bacterium to adapt to granuloma conditions. These lipid modifications were then correlated with the biophysical properties of the mycomembrane, which may affect interactions with antibiotics. Overall, our findings offer a deeper understanding of the bacterial adaptations during dormancy, highlighting the role of lipids in modulating membrane behaviour and drug permeability, ultimately providing the groundwork for the development of more effective treatments tailored to combat latent infections.
目前治疗结核病的方法主要针对（）感染，常常忽视潜伏性结核感染（LTBI）这一新兴问题，其特点是对抗生素敏感性降低。细菌在宿主肉芽肿内休眠期间会经历多种适应性变化，导致产生耐抗生素菌株。分枝杆菌膜在药物通透性方面起着关键作用，本研究旨在通过对在不同培养基和生长阶段培养的细菌进行广泛的脂质组学分析，来表征休眠期间膜脂质的偏差。结果表明，特定脂质定位于膜包膜的不同区域，使细菌能够适应肉芽肿环境。然后将这些脂质修饰与菌膜的生物物理特性相关联，这可能会影响与抗生素的相互作用。总体而言，我们的研究结果为深入了解细菌在休眠期间的适应性变化提供了依据，突出了脂质在调节膜行为和药物通透性方面的作用，最终为开发更有效的治疗潜伏感染的方法奠定了基础。
