Bordetella pertussis fur Gene Restores Iron Repressibility of Siderophore and Protein Expression to Deregulated

We report the isolation and preliminary phenotypic characterization of manganese-resistant Bordetella bronchiseptica mutants with respect to deregulation of siderophore and iron-regulated protein expression. The fur gene of Bordetella pertussis was cloned by genetic complementation of this deregulated phenotype and confirmed as fur by nucleotide sequence analysis. In the host, iron-binding proteins withhold iron from dis-ease-causing microorganisms (34), suppressing their prolifera-tion. Hence, the ability of a microorganism to overcome this host defense mechanism can be considered a virulence trait. Furthermore, expression of a number of bacterial products contributing to infectious disease pathology is elevated in re-sponse to iron limitation (7, 23, 29). Mechanisms of iron acquisition by members of the genus Bordetella are not well understood. All Bordetella species with the exception of Bordetella avium have been shown to excrete putative hydroxamate-type siderophores in response to iron starvation (12), and there is evidence in B. pertussis and B. bronchiseptica of a cell-associated siderophore-independent iron uptake system allowing direct iron removal from the host iron-binding proteins transferrin and lactoferrin (22, 24). In characterized bacterial systems, iron-regulated gene ex-pression is governed principally by the DNA-binding repressor protein Fur (3). Fur homologs have been reported for at least 13 species of gram-negative bacteria, including Escherichia col