Glycopeptidolipids, a Double-Edged Sword of the Mycobacterium abscessus Complex

Abstract

Mycobacterium abscessus is a rapidly-growing species causing a diverse panel of clinical manifestations, ranging from cutaneous infections to severe respiratory disease. Its unique cell wall, contributing largely to drug resistance and to pathogenicity, comprises a vast panoply of complex lipids, among which the glycopeptidolipids (GPLs) have been the focus of intense research. These lipids fulfill various important functions, from sliding motility or biofilm formation to interaction with host cells and intramacrophage trafficking. Being highly immunogenic, the induction of a strong humoral response is likely to select for rough low-GPL producers. These, in contrast to the smooth high-GPL producers, display aggregative properties, which strongly impacts upon intracellular survival. A propensity to grow as extracellular cords allows these low-GPL producing bacilli to escape the innate immune defenses. Transitioning from high-GPL to low-GPL producers implicates mutations within genes involved in biosynthesis or transport of GPL. This leads to induction of an intense pro-inflammatory response and robust and lethal infections in animal models, explaining the presence of rough isolates in patients with decreased pulmonary functions. Herein, we will discuss how, thanks to the generation of defined GPL mutants and the development of appropriate cellular and animal models to study pathogenesis, GPL contribute to M. abscessus biology and physiopathology.

Cyclipostins and Cyclophostin Analogues as Multitarget Inhibitors That Impair Growth of Mycobacterium abscessus

“…14 M. abscessus displays rough (R) and smooth (S) colony morphotypes. [20][21] The S morphotype is related to the abundance of the surface-associated glycopeptidolipids (GPL), which is associated with sliding motility and biofilm formation. 20 In contrast, a remarkable reduction in GPL amount in the cell wall of the R variant was correlated with cord formation.…”

Mycobacterium abscessus Cells Have Altered Antibiotic Tolerance and Surface Glycolipids in Artificial Cystic Fibrosis Sputum Medium

“…While we currently lack a comprehensive model of the chemical and genetic basis of M. abscessus biofilm formation, it is clear that surface glycolipids are important. Glycopeptidolipids, which are found on the outer leaflet of the mycobacterial outer membrane, have been shown to affect biofilm structure (19) and are thought to modulate the course of infection (20,21). Trehalose dimycolate (TDM), which is known to contribute to virulence in Mycobacterium tuberculosis (22), is also found on the surfaces of some M. abscessus strains, though its contribution to biofilm formation and virulence in M. abscessus has not been studied.…”

Mechanical Forces between Mycobacterial Antigen 85 Complex and Fibronectin

“…We concentrate on M. abscessus, an emerging, human-transmissible, multidrug-resistant pathogen causing severe lung infections in cystic fibrosis patients, often resulting in poor treatment outcomes [27,28]. Like other nontuberculous mycobacteria, M. abscessus presents as two different morphological forms, i.e., a smooth (S) morphotype characterized by smooth, dome-shaped, mucoid colonies and homogenously dispersed liquid cultures, and a rough (R) morphotype characterized by rough, dry, wrinkled colonies and highly aggregated liquid cultures [29]. In addition to distinct phenotypic differences in vitro, the S and R morphological distinction also has clinical relevance as the R morphotype tends to cause much worse and more persistent infections than the S type [30,31].…”