Inhalation of Burkholderia thailandensis results in lethal necrotizing pneumonia in mice: a surrogate model for pneumonic melioidosis.

Abstract

Burkholderia thailandensis is closely related to B. pseudomallei, the causative agent of melioidosis, a lethal tropical disease. Burkholderia thailandensis is largely avirulent in humans and, unlike B. pseudomallei, does not require strict biocontainment conditions for study. Because it may be a useful research surrogate for B. pseudomallei, we developed a murine model of airborne B. thailandensis infection. In both C57BL/6 and BALB/c mice, deposition of 103 colony-forming units (CFU)/lung or less of B. thailandensis was non-lethal and infection was readily controlled. Compared with C57BL/6 mice, BALB/c mice exhibited modest resistance to infection after deposition of 10(4) CFU/lung. Deposition of 10(5) CFU/lung resulted in disseminated infection and was universally fatal by 3d. This dose induced robust pulmonary neutrophilia, production of inflammatory cytokines, and elevated serum markers of distant organ injury. Histology demonstrated multiple small foci of necrotizing pneumonia but lung architecture was otherwise preserved, suggesting that respiratory failure is not the cause of death. These findings demonstrate that airborne B. thailandensis infection in mice provides an accessible surrogate model of melioidosis.