Establishment and Validation of Galleria mellonella as a Novel Model Organism To Study Mycobacterium abscessus Infection, Pathogenesis, and Treatment.

Abstract

Treatment of Mycobacterium abscessus infections is extremely challenging due to its intrinsic resistance to most antibiotics, and research of pathogenesis is limited due to a lack of a practical in vivo model of infection. The objective of this study was to establish a simple in vivo model for M. abscessus infection, virulence, and drug testing in Galleria mellonella larvae. We inoculated larvae with M. abscessus bacteria and assessed histopathology, CFU count, and mortality with and without antibiotic treatment. We also constructed a luminescent, recombinant M. abscessus mutant, mDB158, and imaged infected larvae using the IVIS in vivo imaging system. M. abscessus proliferated and induced granuloma-like responses in infected larvae, leading to larval mortality. The G. mellonella model was further validated successfully by demonstration of the expected favorable antimicrobial effect of treatment with meropenem and the superiority of combination treatment (meropenem and tigecycline) over that with single agents. We then used IVIS imaging of larvae infected with luminescent M. abscessus, allowing live real-time assessment of bacterial load. We used this method to compare the antimicrobial effects of various antibiotics (meropenem, amikacin, linezolid, levofloxacin, etc.) on bacterial proliferation and larval survival. Meropenem and amikacin had the most favorable effects, correlating well with common clinical practice guidelines. These findings suggest G. mellonella to be an excellent in vivo model for research of M. abscessus infection, pathogenesis, and treatment. Luminescent M. abscessus and IVIS imaging further facilitates this model. Results obtained in this model clearly substantiated common clinical practice, thus validating the model as a predictor of treatment efficacy and outcome.