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Please use this identifier to cite or link to this item: http://hdl.handle.net/123456789/13420

Title: Microbiological, Histological, Immunological, and Toxin Response to Antibiotic Treatment in the Mouse Model of Mycobacterium ulcerans Disease
Authors: Sarfo, Fred Stephen
Converse, Paul J.
Almeida, Deepak V.
Zhang, Jihui
Robinson, Clive
Wansbrough-Jones, Mark
Grosset, Jacques H.
Issue Date: 2013
Publisher: Plos Neglected Tropical Diseases
Citation: Sarfo FS, Converse PJ, Almeida DV, Zhang J, Robinson C, et al. (2013) Microbiological, Histological, Immunological, and Toxin Response to Antibiotic Treatment in the Mouse Model of Mycobacterium ulcerans Disease. PLoS Negl Trop Dis 7(3): e2101. doi:10.1371/journal.pntd.0002101
Abstract: Mycobacterium ulcerans infection causes a neglected tropical disease known as Buruli ulcer that is now found in poor rural areas of West Africa in numbers that sometimes exceed those reported for another significant mycobacterial disease, leprosy, caused by M. leprae. Unique among mycobacterial diseases, M. ulcerans produces a plasmid-encoded toxin called mycolactone (ML), which is the principal virulence factor and destroys fat cells in subcutaneous tissue. Disease is typically first manifested by the appearance of a nodule that eventually ulcerates and the lesions may continue to spread over limbs or occasionally the trunk. The current standard treatment is 8 weeks of daily rifampin and injections of streptomycin (RS). The treatment kills bacilli and wounds gradually heal. Whether RS treatment actually stops mycolactone production before killing bacilli has been suggested by histopathological analyses of patient lesions. Using a mouse footpad model of M. ulcerans infection where the time of infection and development of lesions can be followed in a controlled manner before and after antibiotic treatment, we have evaluated the progress of infection by assessing bacterial numbers, mycolactone production, the immune response, and lesion histopathology at regular intervals after infection and after antibiotic therapy. We found that RS treatment rapidly reduced gross lesions, bacterial numbers, and ML production as assessed by cytotoxicity assays and mass spectrometric analysis. Histopathological analysis revealed that RS treatment maintained the association of the bacilli with (or within) host cells where they were destroyed whereas lack of treatment resulted in extracellular infection, destruction of host cells, and ultimately lesion ulceration. We propose that RS treatment promotes healing in the host by blocking mycolactone production, which favors the survival of host cells, and by killing M. ulcerans bacilli.
Description: An article published by Sarfo FS, Converse PJ, Almeida DV, Zhang J, Robinson C, et al. (2013) Microbiological, Histological, Immunological, and Toxin Response to Antibiotic Treatment in the Mouse Model of Mycobacterium ulcerans Disease. PLoS Negl Trop Dis 7(3): e2101. doi:10.1371/journal.pntd.0002101
URI: http://hdl.handle.net/123456789/13420
Appears in Collections:College of Health Sciences

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