<i>Mycobacterium marinum</i> as a model for understanding principles of mycobacterial pathogenesis.
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2025-05
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Mycobacterium marinum is a fish pathogen that has become a powerful and well-established model that has accelerated our understanding of the mechanisms of mycobacterial disease. M. marinum is a versatile surrogate for understanding the closely related human pathogen M. tuberculosis, which causes tuberculosis in humans. M. marinum has defined key mechanisms of pathogenesis, both shared with M. tuberculosis and unique to this species. In this review, we discuss the discovery of M. marinum as an occasional human pathogen, the shared aspects of pathogenesis with M. tuberculosis, and how M. marinum has been exploited as a model to define the molecular mechanisms of mycobacterial pathogenesis across several phases of infection.
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Menon, Aruna R, Rebecca J Prest, David M Tobin and Patricia A Champion (2025). <i>Mycobacterium marinum</i> as a model for understanding principles of mycobacterial pathogenesis. Journal of bacteriology, 207(5). p. e0004725. 10.1128/jb.00047-25 Retrieved from https://hdl.handle.net/10161/35400.
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Scholars@Duke
Aruna Menon
David M. Tobin
Tuberculosis: Mycobacterial Pathogenesis and Host Susceptibility
Tuberculosis kills 1.5 million people annually. Our laboratory aims to understand the intricate interplay between mycobacteria and their hosts using a combination of model organism genetics, human genetics, pharmacology and high-resolution microscopy. By identifying key pathways utilized by the infecting bacteria and the host innate immune system, we hope to discover new therapeutic targets and interventions to combat this enduringly destructive disease.
Using a Mycobacterium/zebrafish model, we have identified new host susceptibility loci for tuberculosis. Zebrafish are natural hosts to Mycobacterium marinum, the closest relative of the Mycobacterium tuberculosis complex. Because zebrafish embryos and larvae are optically transparent, we are able to visualize the complex details of mycobacterial pathogenesis in whole, live animals. The facile genetics of the zebrafish allow us to map and positionally clone affected host susceptibility genes. In addition, zebrafish larvae are remarkably permeable to small molecules, providing a platform for whole-animal pharmacological manipulation of specific host immune responses.
We have identified novel pathways that modulate susceptibility to tuberculosis. We have shown that genes identified in the zebrafish model are also important in human tuberculosis. We find robust associations of human variants in a specific eicosanoid pathway with susceptibility to both tuberculosis and leprosy.
We have active collaborations in both Vietnam and Guatemala. In Guatemala, we are working with the Clínica Familiar Luis Angel García and the Asociación de Salud Integral to support projects involving HIV-infected patients and to understand the dynamics of TB transmission in Central America.
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