Marsollier Laurent, Brodin Priscille, Jackson Mary, Korduláková Jana, Tafelmeyer Petra, Carbonnelle Etienne, Aubry Jacques, Milon Geneviève, Legras Pierre, André Jean-Paul Saint, Leroy Céline, Cottin Jane, Guillou Marie Laure Joly, Reysset Gilles, Cole Stewart T
Unité de Génétique Moléculaire Bactérienne, Institut Pasteur, Paris, France.
PLoS Pathog. 2007 May 4;3(5):e62. doi: 10.1371/journal.ppat.0030062.
The role of biofilms in the pathogenesis of mycobacterial diseases remains largely unknown. Mycobacterium ulcerans, the etiological agent of Buruli ulcer, a disfiguring disease in humans, adopts a biofilm-like structure in vitro and in vivo, displaying an abundant extracellular matrix (ECM) that harbors vesicles. The composition and structure of the ECM differs from that of the classical matrix found in other bacterial biofilms. More than 80 proteins are present within this extracellular compartment and appear to be involved in stress responses, respiration, and intermediary metabolism. In addition to a large amount of carbohydrates and lipids, ECM is the reservoir of the polyketide toxin mycolactone, the sole virulence factor of M. ulcerans identified to date, and purified vesicles extracted from ECM are highly cytotoxic. ECM confers to the mycobacterium increased resistance to antimicrobial agents, and enhances colonization of insect vectors and mammalian hosts. The results of this study support a model whereby biofilm changes confer selective advantages to M. ulcerans in colonizing various ecological niches successfully, with repercussions for Buruli ulcer pathogenesis.
生物膜在分枝杆菌病发病机制中的作用在很大程度上仍不明确。溃疡分枝杆菌是人类致残性疾病布氏溃疡的病原体，在体外和体内均呈现出类似生物膜的结构，具有丰富的胞外基质（ECM），其中含有囊泡。ECM的组成和结构不同于其他细菌生物膜中的经典基质。该胞外区室中存在80多种蛋白质，似乎参与应激反应、呼吸作用和中间代谢。除了大量的碳水化合物和脂质外，ECM还是聚酮毒素分枝杆菌内酯的储存库，分枝杆菌内酯是迄今为止已确定的溃疡分枝杆菌唯一的毒力因子，从ECM中提取的纯化囊泡具有高度细胞毒性。ECM使分枝杆菌对抗菌剂的抗性增强，并促进其在昆虫媒介和哺乳动物宿主中的定殖。本研究结果支持一种模型，即生物膜变化赋予溃疡分枝杆菌在成功定殖各种生态位方面的选择性优势，这对布氏溃疡的发病机制具有影响。
