title: Experimental infection of the pig with Mycobacterium ulcerans: a novel model for studying the pathogenesis of Buruli ulcer disease.
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.
  
  
  RESULTS
  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 × 10(7) and 2 × 10(6) 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Swiss Tropical and Public Health Institute, Basel, Switzerland; University of Basel, Basel, Switzerland.
authors.forename: Miriam
authors.initials: M
authors.lastname: Bolz
authors.affiliation: Institute of Virology and Immunology (IVI), Mittelhäusern, Switzerland.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Ruggli
authors.affiliation: Swiss Tropical and Public Health Institute, Basel, Switzerland; University of Basel, Basel, Switzerland.
authors.forename: Marie-Thérèse
authors.initials: MT
authors.lastname: Ruf
authors.affiliation: Institute of Virology and Immunology (IVI), Mittelhäusern, Switzerland.
authors.forename: Meret E
authors.initials: ME
authors.lastname: Ricklin
authors.affiliation: Institute of Virology and Immunology (IVI), Mittelhäusern, Switzerland.
authors.forename: Gert
authors.initials: G
authors.lastname: Zimmer
authors.affiliation: Swiss Tropical and Public Health Institute, Basel, Switzerland; University of Basel, Basel, Switzerland.
authors.forename: Gerd
authors.initials: G
authors.lastname: Pluschke
mesh_terms: D000818:Animals; D054312:Buruli Ulcer; D004195:Disease Models, Animal; D019911:Mycobacterium ulcerans; D013552:Swine