Mycobacterium abscessus: Shapeshifter of the Mycobacterial World

Abstract

In this review we will focus on unique aspects of Mycobacterium abscessus (MABS) which we feel earn it the designation of "shapeshifter of the mycobacterial world." We will review its emergence as a distinct species, the recognition and description of MABS subspecies which are only now being clearly defined in terms of pathogenicity, its ability to exist in different forms favoring a saprophytic lifestyle or one more suitable to invasion of mammalian hosts, as well as current challenges in terms of antimicrobial therapy and future directions for research. One can see in the various phases of MABS, a species transitioning from a free living saprophyte to a host-adapted pathogen.

Keywords: bronchiectasis; cystic fibrosis; fibroblasts; glycopeptidolipid; serpentine cording; toll-like receptor 2.

FIGURE 1

Environmental Mycobacterium abscessus (MABS) isolates have the smooth colony morphotype and express glycopeptidolipid (GPL). GPL in the outermost aspect of the cell wall “masks” underlying glycosylated lipoproteins such as phosphatidyl-myo-inositol mannosides (PIMs) involved in immune recognition and blocks the bacterial cell–cell interaction of lipids such trehalose polyphleates which may play a role in clumping and cord formation. By preventing MABS from being recognized by innate immune surveillance mechanisms and promoting biofilm formation, GPL facilitates colonization of bronchiectatic lung airways. After colonization, spontaneous or temperature sensitive loss of GPL is associated with “unmasking” of these molecules. This leads to recognition by TLR2 on macrophages and respiratory epithelial cells resulting in release of the proinflammatory cytokines TNFα (from macrophages) and IL-8 (from respiratory epithelial cells). Rough variants acquire a virulent phenotype characterized by the ability to grow in serpentine cords and cause macrophage apoptosis leading to rapid cell–cell spread and propagation of infection. Isolation of MABS rough variants from the sputum is associated with progressive lung infection.