The Pathological Effect of the Bordetella Dermonecrotic Toxin in Mice

Abstract

The effect of dermonecrotic toxin (DNT) expression of Bordetella bronchiseptica was studied in mice by comparing the pathology induced by a wild type strain with that induced by an isogenic DNT- strain in which part of the structural gene has been replaced by an antibiotic resistance cassette. While extracts of strain B58 proved toxic in intravenously inoculated mice, similar extracts from strain B58GP had lost toxic activity. The parent (B58) and the mutant (B58GP) strains of B. bronchiseptica each possessed comparable virulence for mice. These findings confirmed that DNT production was successfully abolished in strain B58GP while other virulence characteristics required for pathogenicity in mice remained intact, at a comparable level to the parent strain. Turbinate atrophy was observed in mice infected with the DNT+ strain, but not in those infected with the DNT-strain. This indicates that DNT is the cause of turbinate atrophy in the mice and not other factors produced by phase I strains of B. bronchiseptica. B. bronchiseptica DNT showed a lienotoxic effect (lymphocyte depletion and a reduction in the intensity of extramedullar haemocytopoieis) that is considered to adversely alter the immune function of the host animal. In mice infected with strain B58GP, catarrhal pneumonia with characteristic lympho-histiocytic peribronchial and perivascular infiltration was noticed. In mice infected with strain B58, large necrotic areas were seen surrounded by an inflammatory reaction. The DNT appears to directly damage lung tissues, at least in mice. DNT production seems to enhance the establishment of B. bronchiseptica in the lungs, presumably by reducing the local resistance and causing severe local damage to the lung tissues.