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- Title
Experimental Infection of the Pig with Mycobacterium ulcerans: A Novel Model for Studying the Pathogenesis of Buruli Ulcer Disease.
- Authors
Bolz, Miriam; Ruggli, Nicolas; Ruf, Marie-Thérèse; Ricklin, Meret E.; Zimmer, Gert; Pluschke, Gerd
- Abstract
Background: Buruli ulcer (BU) is a slowly progressing, necrotising disease of the skin caused by infection with Mycobacterium ulcerans. Non-ulcerative manifestations are nodules, plaques and oedema, which may progress to ulceration of large parts of the skin. Histopathologically, BU is characterized by coagulative necrosis, fat cell ghosts, epidermal hyperplasia, clusters of extracellular acid fast bacilli (AFB) in the subcutaneous tissue and lack of major inflammatory infiltration. The mode of transmission of BU is not clear and there is only limited information on the early pathogenesis of the disease available. Methodology/Principal Findings: For evaluating the potential of the pig as experimental infection model for BU, we infected pigs subcutaneously with different doses of M. ulcerans. The infected skin sites were excised 2.5 or 6.5 weeks after infection and processed for histopathological analysis. With doses of 2×107 and 2×106 colony forming units (CFU) we observed the development of nodular lesions that subsequently progressed to ulcerative or plaque-like lesions. At lower inoculation doses signs of infection found after 2.5 weeks had spontaneously resolved at 6.5 weeks. The observed macroscopic and histopathological changes closely resembled those found in M. ulcerans disease in humans. Conclusion/Significance: Our results demonstrate that the pig can be infected with M. ulcerans. Productive infection leads to the development of lesions that closely resemble human BU lesions. The pig infection model therefore has great potential for studying the early pathogenesis of BU and for the development of new therapeutic and prophylactic interventions. Author Summary: Buruli ulcer caused by Mycobacterium ulcerans infection is a necrotizing disease of the skin and the underlying subcutaneous tissue. Since the skin of pigs (Sus scrofa) has striking structural and physiological similarities with human skin, we investigated whether it is possible to develop an experimental M. ulcerans infection model by subcutaneous injection of the mycobacteria into pig skin. Injection of 2×106 or 2×107 colony forming units of M. ulcerans led to the development of lesions that were both macroscopically and microscopically very similar to human Buruli ulcer lesions. In particular for the characterization of the pathogenesis of Buruli ulcer and of immune defence mechanisms against M. ulcerans, the pig model appears to be superior to the mouse foot pad model commonly used for the evaluation of the efficacy of chemotherapeutic regimens.
- Subjects
BURULI ulcer; MYCOBACTERIAL diseases; FAT cells; SUBCUTANEOUS injections; WILD boar; SKIN diseases
- Publication
PLoS Neglected Tropical Diseases, 2014, Vol 8, Issue 7, p1
- ISSN
1935-2727
- Publication type
Article
- DOI
10.1371/journal.pntd.0002968