本期文章：《细胞》：Online/在线发表

德国海德堡大学Vivek V. Thacker小组揭示生物膜样结核分枝杆菌索的机械病理学。2023年10月20日，《细胞》杂志在线发表了这项成果。

据研究人员介绍，结核分枝杆菌（Mtb）在去垢剂的轴向培养过程中会形成生物膜样索，这是一种临床毒力标识。

在肺芯片（LoC）和小鼠模型中，肺泡细胞中的菌索通过核压缩抑制先天性免疫信号。此后，细胞外的索会导致依赖接触的吞噬细胞死亡，但会在上皮细胞间生长。这些机械病理机制的缺失解释了为什么在细胞外索缺失的Mtb感染中，肺泡病变的比例更高，且免疫浸润和传播缺陷增加。压缩Mtb脂质单层会诱发相变，从而实现机械能储存。

基于代理的模拟结果表明，能量储存能力的提高足以形成在机械扰动下仍能保持结构完整性的菌索。即使暴露在抗生素环境中，菌索中的细菌仍能保持翻译活性，并在治疗停止后迅速再生。这项研究为结核病感染中的生物物理和功能以及索结构的治疗提供了一个概念框架，它与单个细菌的机制无关。

附：英文原文

Title: Mechanopathology of biofilm-like Mycobacterium tuberculosis cords

Author: Richa Mishra, Melanie Hannebelle, Vishal P. Patil, Analle Dubois, Cristina Garcia-Mouton, Gabriela M. Kirsch, Maxime Jan, Kunal Sharma, Nicolas Guex, Jessica Sordet-Dessimoz, Jesus Perez-Gil, Manu Prakash, Graham W. Knott, Neeraj Dhar, John D. McKinney, Vivek V. Thacker

Issue&Volume: 2023-10-20

Abstract: Mycobacterium tuberculosis (Mtb) cultured axenically without detergent forms biofilm-like cords, a clinical identifier of virulence. In lung-on-chip (LoC) and mouse models, cords in alveolar cells contribute to suppression of innate immune signaling via nuclear compression. Thereafter, extracellular cords cause contact-dependent phagocyte death but grow intercellularly between epithelial cells. The absence of these mechanopathological mechanisms explains the greater proportion of alveolar lesions with increased immune infiltration and dissemination defects in cording-deficient Mtb infections. Compression of Mtb lipid monolayers induces a phase transition that enables mechanical energy storage. Agent-based simulations demonstrate that the increased energy storage capacity is sufficient for the formation of cords that maintain structural integrity despite mechanical perturbation. Bacteria in cords remain translationally active despite antibiotic exposure and regrow rapidly upon cessation of treatment. This study provides a conceptual framework for the biophysics and function in tuberculosis infection and therapy of cord architectures independent of mechanisms ascribed to single bacteria.

DOI: 10.1016/j.cell.2023.09.016