pyochelin and Lung-Diseases

Previously, orbA, the gene encoding the outer membrane receptor for ferric-ornibactin, was identified in Burkholderia cenocepacia K56-2, a strain which produces ornibactin, salicylic acid, and negligible amounts of pyochelin. A K56-2 orbA mutant was less virulent than the parent strain in a rat agar bead infection model. In this study, an orbA mutant of B. cenocepacia Pc715j which produces pyochelin in addition to ornibactin and salicylic acid was constructed. The gene encoding the outer membrane receptor for ferric-pyochelin (fptA) was also identified. An fptA mutant was constructed in Pc715j and shown to be deficient in [(59)Fe]pyochelin uptake. A 75-kDa iron-regulated protein was identified in outer membrane preparations of Pc715j that was absent in outer membrane preparations of Pc715jfptA::tp. Pc715jfptA::tp and Pc715jorbA::tp produced smaller amounts of their corresponding siderophores. Both Pc715jorbA::tp and Pc715jfptA::tp were able to grow in iron starvation conditions in vitro. In the agar bead model, the Pc715jorbA::tp mutant was cleared from the lung, indicating that the pyochelin uptake system does not compensate for the absence of a functional ornibactin system. Pc715jfptA::tp persisted in rat lung infections in numbers similar to those of the parent strain, indicating that the ferric-ornibactin uptake system could compensate for the defect in ferric-pyochelin uptake in vivo. These studies suggest that the ornibactin uptake system is the most important siderophore-mediated iron transport system in B. cenocepacia lung infections.

Topics: Animals; Biological Transport, Active; Burkholderia cepacia complex; Burkholderia Infections; Genes, Bacterial; Iron; Lung Diseases; Male; Mutation; Oligopeptides; Phenols; Rats; Rats, Sprague-Dawley; Siderophores; Thiazoles; Virulence

Exogenously supplied pyochelin influenced the virulence of Pseudomonas cepacia pyochelin-negative strains in a chronic pulmonary infection model in rats. Groups of rats were inoculated transtracheally with agar beads containing P. cepacia or P. aeruginosa strains, saturated with either pyochelin or PBS. Supplementation of the inocula with pyochelin had no effect on the number of bacteria recovered from the lungs. The availability of pyochelin, however, increased the degree of pathology observed in lungs infected with pyochelin-negative strains of P. cepacia. The area of pathological involvement in the lung was about 2-fold larger, when pyochelin was present. Inclusion of pyochelin in the inoculum had no effect on the degree of pathology observed in lungs infected with a pyochelin-positive P. aeruginosa strain. Pyochelin was shown to stimulate in vitro growth of P. cepacia, but it had no effect on production of lipase or protease, factors which may be involved in P. cepacia virulence. These studies support our hypothesis that pyochelin may be important for dissemination in P. cepacia infections.

Topics: Animals; Lung Diseases; Phenols; Pseudomonas; Pseudomonas Infections; Rats; Thiazoles