Non-pigmented rapidly growing mycobacteria smooth and rough colony phenotypes pathogenicity evaluated usingin vitroand experimental models

Abstract

Non-pigmented rapidly growing mycobacteria (NPRGM) are widely distributed in water, soil and animals. It has been observed an increasing importance of NPRGM related-infections, particularly due to the high antimicrobial resistance. NPRGM have rough and smooth colony phenotypes, and several studies have showed that rough colony variants are more virulent than smooth ones. However, other studies have failed to validate this observation. In this study, we have performed two models, invitro and in vivo, in order to assess the different pathogenicity of these two phenotypes. We used collection and clinical strains of Mycobacteriumabscessus, Mycobacterium fortuitum and Mycobacteriumchelonae. On the invitro model (macrophages), phagocytosis was higher for M. abscessus and M. fortuitum rough colony variant strains when compared to smooth colony variants. However, we did not find differences with colonial variants of M. chelonae. Survival of Galleriamellonella larvae in the experimental model was lower for M. abscessus and M. fortuitum rough colony variants when compared with larvae infected with smooth colony variants. We did not find differences in larvae infected with M. chelonae.Results of our in vivo study correlated well with the experimental model. This fact could have implications on the interpretation of the clinical significance of the NPRGM isolate colonial variants.

Updated Review on the Mechanisms of Pathogenicity in Mycobacterium abscessus, a Rapidly Growing Emerging Pathogen

“…More recently, Roux et al [ 18 ] used a macrophage cell culture model and showed that R M. abscessus cells were able to multiply inside the cells, while S cells were not. This model has been used more recently with other species, showing that the R strains of both M. abscessus and other RGM can survive inside the macrophages more easily than the S strains [ 25 ].…”

“…Moreover, studies evaluating murine models described a limited ability to induce chronic infection that simulates pulmonary infection in humans [ 29 ]. Therefore, alternative non-mammalian models, such as Galleria mellonella moth larvae, Drosophila melanogaster, and zebrafish embryos have been developed to study both host and mycobacterial determinants of pathogenesis during chronic infection with M. abscessus [ 25 , 29 , 30 ].…”

“…Another invertebrate model, Galleria mellonella, is a reproducible, low-cost, and ethically acceptable in vivo model that is increasingly recognized as an alternative to studying microbial infections [ 25 , 28 ]. This model has been used to study the pathogenicity and virulence of M. tuberculosis and other NTM infections.…”

Alternatives to Antibiotics against Mycobacterium abscessus

“…Rough colonies induce a proinflammatory response as part of a severe infection resulting in massive tissue destruction [ 17 ]. Different in vivo models have shown that rough morphotypes are more virulent than smooth variants [ 18 , 19 , 20 ].…”

CFTR Depletion Confers Hypersusceptibility to Mycobacterium fortuitum in a Zebrafish Model

“…A murine neutropenic model, in which neutropenia is induced by intraperitoneal doses of cyclophosphamide, has also been exploited to demonstrate the in vivo efficacy of drugs against M. fortuitum and M. abscessus (Das et al, 2019). In addition, a recent study highlighted the suitability of the Galleria mellonella moth larvae as a cheap, efficient and rapid in vivo model for the screening of antibiotic combinations and novel treatments against NTM, including M. fortuitum (Entwistle and Coote, 2018;García-Coca et al, 2019).…”