Establishment and validation of Galleria mellonella as a novel model organism to study Mycobacterium abscessus infection, pathogenesis and treatment. [PublishAheadOfPrint]

Introduction: 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.

Objectives: To establish a simple in-vivo model for M. abscessus infection, virulence, and drug testing in G. mellonella larvae.

Methods: We inoculated larvae with M. abscessus, and followed histopathology, CFU count and mortality with and without antibiotic treatment. We also constructed a luminescent, recombinant M. abscesssus, mDB158, and imaged infected larvae using IVIS®.

Results: M. abscessus proliferated and induced granulomatous-like responses in infected larvae leading to larval mortality. The G. mellonella model was further successfully validated by demonstration of the expected favorable antimicrobial effect of treatment with meropenem, and the superiority of combination treatment (meropenem and tigecycline) over 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 effect of various antibiotics (meropemen, amikacin, linezolid, levofloxacin, etc.) on bacterial proliferation and larval survival. Meropenem and amikacin had the most favorable effect, correlating well with common clinical practice guidelines.

Conclusions: 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.

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