Comparative survival of environmental and clinical Mycobacterium abscessus isolates in a variety of diverse host cells

Abstract

Aims: Mycobacterium abscessus subsp. abscessus (MABS) is an emerging, opportunistic pathogen found globally in freshwater biofilms and soil. Typically, isolates are treated as a uniform group of organisms and very little is known about their comparative survival in healthy host cells. We posit that environmentally-and clinically derived isolates, show differential infectivity in immune cells and resistance to innate defenses.Methods and Results: Six MABS isolates were tested including three water biofilm/ soil and three sputum-derived isolates. A clinical MABS type strain and an environmental isolate of Arthrobacter were also included. MABS counts were significantly higher compared to Arthrobacter after co-culture with Acanthamoeba lenticulata, BEAS-2B epithelial cells, alveolar macrophages and the THP-1 macrophage cell line.A rough sputum-derived MABS isolate emerged as an isolate with higher virulence compared to others tested, as both a pellicle and cord former, survivor in the human cell models tested, inducer of high and prolonged production of pro-inflammatory cytokines, and the capacity to evade LL-37. Conclusions: Findings support intraspecies variation between MABS isolates. Significance and Impact of the Study: These data indicate subversion of host immune defenses by environmental and clinical MABS isolates is nuanced and maybe isolate dependent, providing new information regarding the pathogenesis of NTM infections.

Cell envelope remodeling requires high concentrations of biotin during Mycobacterium abscessus model lung infection

“…Thus, examining genes required for M. abscessus infection in a system that models the lung environment may highlight new pathways to target with antibiotics. Many studies have scrutinized how M. abscessus behaves in phagocytic cells such as macrophages [29][30][31][32][33][34][35] , and a variety of animal models have been developed for M. abscessus infection [36][37][38][39][40][41][42][43] ; however, these systems often represent systemic or invasive disease, and typically do not recapitulate the extracellular, luminal niche occupied by M. abscessus during human lung infection. Tissue culture systems represent an alternative approach to model lung infection, and can be successfully applied to M. abscessus [44][45][46][47] .…”