Adusumilli Sarojini, Mve-Obiang Armand, Sparer Tim, Meyers Wayne, Hayman John, Small Pamela Long Claus
Microbiology Department, University of Tennessee, Knoxville, TN, USA.
Cell Microbiol. 2005 Sep;7(9):1295-304. doi: 10.1111/j.1462-5822.2005.00557.x.
Mycobacterium ulcerans produces an extracellular cutaneous infection (Buruli ulcer) characterized by immunosuppression. This is in stark contrast to all other pathogenic Mycobacteria species that cause intracellular, granulomatous infections. The unique mycobacterial pathology of M. ulcerans infection is attributed to a plasmid-encoded immunomodulatory macrolide toxin, mycolactone. In this article we explore the role of mycolactone in the virulence of M. ulcerans using mycolactone and genetically defined mycolactone negative mutants. In a guinea pig infection model wild-type (WT) M. ulcerans produces an extracellular infection whereas mycolactone negative mutants produce an intracellular inflammatory infection similar to that of Mycobacterium marinum. Although mycolactone negative mutants are avirulent, they persist for at least 6 weeks. Chemical complementation of M. ulcerans mutants with mycolactone restores WT M. ulcerans pathology. Mycolactone negative mutants are capable of growth within macrophages in vitro whereas macrophages are killed by WT M. ulcerans. The ability of mycolactone to caused delayed cell death via apoptosis has been reported. However, mycolactone also causes cell death via necrosis. In vitro mycolactone has antiphagocytic properties. Neither WT M. ulcerans nor mycolactone negative strains are strong neutrophil attractants. These results suggest that mycolactone is largely responsible for the unique pathology produced by M. ulcerans.
溃疡分枝杆菌会引发一种以免疫抑制为特征的细胞外皮肤感染（布氏溃疡）。这与所有其他引起细胞内肉芽肿性感染的致病性分枝杆菌物种形成了鲜明对比。溃疡分枝杆菌感染独特的分枝杆菌病理学特征归因于一种质粒编码的免疫调节大环内酯毒素——毒素内酯。在本文中，我们使用毒素内酯和基因定义的毒素内酯阴性突变体来探究毒素内酯在溃疡分枝杆菌毒力中的作用。在豚鼠感染模型中，野生型（WT）溃疡分枝杆菌会引发细胞外感染，而毒素内酯阴性突变体则会引发类似于海分枝杆菌的细胞内炎性感染。尽管毒素内酯阴性突变体无毒力，但它们至少能持续存在6周。用毒素内酯对溃疡分枝杆菌突变体进行化学互补可恢复野生型溃疡分枝杆菌的病理学特征。毒素内酯阴性突变体在体外能够在巨噬细胞内生长，而野生型溃疡分枝杆菌会杀死巨噬细胞。据报道，毒素内酯能够通过凋亡导致延迟性细胞死亡。然而，毒素内酯也会通过坏死导致细胞死亡。在体外，毒素内酯具有抗吞噬特性。野生型溃疡分枝杆菌和毒素内酯阴性菌株都不是强大的中性粒细胞吸引剂。这些结果表明，毒素内酯在很大程度上导致了溃疡分枝杆菌产生的独特病理学特征。
