TY - JOUR
T1 - In vivo imaging of bioluminescent Mycobacterium ulcerans: A tool to refine the murine buruli ulcer tail model: A tool to refine the murine buruli ulcer tail model
AU - Omansen, Till F.
AU - Marcsisin, Renee A.
AU - Chua, Brendon Y.
AU - Zeng, Weiguang
AU - Jackson, David C.
AU - Porter, Jessica L.
AU - Stienstra, Ymkje
AU - Van Der Werf, Tjip S.
AU - Stinear, Timothy P.
PY - 2019/1/1
Y1 - 2019/1/1
N2 - Buruli ulcer (BU) is a neglected tropical disease caused by infection with Mycobacterium ulcerans. Unclear transmission, no available vaccine, and suboptimal treatment regimens hamper the control of this disease. Carefully designed preclinical research isneeded toaddress these shortcomings. In vivo imaging (IVIS®, Perkin Elmer, Waltham, MA) of infection isan emerging tool that permits monitoringofdisease progression and reduces the needtousing large numbers of miceatdifferent time-points during the experiment, as individual mice can be imaged at multipletime-points. We aimed to further describe the use of in vivo imaging (IVIS) in BU. We studied the detection of M. ulcerans in experimentally infected BALB/c mouse tails and the subsequent histopathology and immune response in this pilot study. IVIS-monitoring was performed weekly in ten infected BALB/cmice to measure light emitted as a proxy for bacterial load. Nine of 10(90%)BALB/c mice infected subcutaneously with 3.3 × 105 M. ulcerans JKD8049 (containing pMV306 hsp16+luxG13) exhibited light emission from the site of infection, indicating M. ulcerans growth in vivo, whereas only five of 10 (50%) animals developed clinical signs of the disease. Specific antibody titers were detected within 2 weeks of the infection. Interferon (IFN)-γ and interleukin (IL)-10 were elevated in animals with pathology. Histopathology revealed clusters of acid-fast bacilli in the subcutaneous tissue, with macrophage infiltration and granuloma formation resembling human BU. Our study successfully showed the utility of M. ulcerans IVIS monitoring and lays a foundation for further research.
AB - Buruli ulcer (BU) is a neglected tropical disease caused by infection with Mycobacterium ulcerans. Unclear transmission, no available vaccine, and suboptimal treatment regimens hamper the control of this disease. Carefully designed preclinical research isneeded toaddress these shortcomings. In vivo imaging (IVIS®, Perkin Elmer, Waltham, MA) of infection isan emerging tool that permits monitoringofdisease progression and reduces the needtousing large numbers of miceatdifferent time-points during the experiment, as individual mice can be imaged at multipletime-points. We aimed to further describe the use of in vivo imaging (IVIS) in BU. We studied the detection of M. ulcerans in experimentally infected BALB/c mouse tails and the subsequent histopathology and immune response in this pilot study. IVIS-monitoring was performed weekly in ten infected BALB/cmice to measure light emitted as a proxy for bacterial load. Nine of 10(90%)BALB/c mice infected subcutaneously with 3.3 × 105 M. ulcerans JKD8049 (containing pMV306 hsp16+luxG13) exhibited light emission from the site of infection, indicating M. ulcerans growth in vivo, whereas only five of 10 (50%) animals developed clinical signs of the disease. Specific antibody titers were detected within 2 weeks of the infection. Interferon (IFN)-γ and interleukin (IL)-10 were elevated in animals with pathology. Histopathology revealed clusters of acid-fast bacilli in the subcutaneous tissue, with macrophage infiltration and granuloma formation resembling human BU. Our study successfully showed the utility of M. ulcerans IVIS monitoring and lays a foundation for further research.
U2 - 10.4269/ajtmh.18-0959
DO - 10.4269/ajtmh.18-0959
M3 - Article
VL - 101
SP - 1312
EP - 1321
JO - The American Journal of Tropical Medicine and Hygiene
JF - The American Journal of Tropical Medicine and Hygiene
IS - 6
ER -
