Mycobacterium abscessuscording prevents phagocytosis and promotes abscess formation

Abstract

Mycobacterium abscessusis a rapidly growingMycobacteriumcausing a wide spectrum of clinical syndromes. It now is recognized as a pulmonary pathogen to which cystic fibrosis patients have a particular susceptibility. TheM. abscessusrough (R) variant, devoid of cell-surface glycopeptidolipids (GPLs), causes more severe clinical disease than the smooth (S) variant, but the underlying mechanisms of R-variant virulence remain obscure. Exploiting the optical transparency of zebrafish embryos, we observed that the increased virulence of theM. abscessusR variant compared with the S variant correlated with the loss of GPL production. The virulence of the R variant involved the massive production of serpentine cords, absent during S-variant infection, and the cords initiated abscess formation leading to rapid larval death. Cording occurred within the vasculature and was highly pronounced in the central nervous system (CNS). It appears thatM. abscessusis transported to the CNS within macrophages. The release ofM. abscessusfrom apoptotic macrophages initiated the formation of cords that grew too large to be phagocytized by macrophages or neutrophils. This study is a description of the crucial role of cording in the in vivo physiopathology ofM. abscessusinfection and emphasizes cording as a mechanism of immune evasion.