The tiny zebrafish has enabled some big advances in biomedical research, thanks in part to its optical transparency during embryonic stages, which allows for direct, microscopic visualization of biological processes in vivo in real time. Its latest contribution is to our understanding of tuberculosis, a disease in which pathogenic mycobacteria induce the formation of complex cellular aggregates called granulomas. In humans, Mycobacterium tuberculosis is the primary pathogen, but tuberculosis is often modeled in zebrafish by infection with the related bacterium Mycobacterium marinum, which results in formation of granulomas that closely resemble those of human tuberculosis.
Stefan Oehlers and David Tobin (Duke University Medical Center, Durham, NC) led the project to characterize granuloma development after mycobacterial infection by microscopic analysis of fluorescently labeled cells in live zebrafish. They observed that granuloma formation was closely linked to angiogenesis (the growth of new blood vessels). The initiation of angiogenesis promoted mycobacterial growth and spread the infection to other tissues. Administration of drugs that inhibit angiogenesis suppressed mycobacterial growth and limited disease spread (Nature doi:10.1038/nature13967; published online 24 November 2014). The authors suggest that these drugs could be used in combination with antibiotics such as rifampicin to treat tuberculosis, particularly in cases where the disease is resistant to current antibiotic regimens. MH
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