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Infect. Immun. doi:10.1128/IAI.00407-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Passively released heme from hemoglobin and myoglobin is a potential source of nutrient iron for Bordetella bronchiseptica

Department of Microbiology and Immunology, The Witebsky Center for Microbial Pathogenesis and Immunology, Department of Oral Biology, The University at Buffalo, and Department of Biochemistry & Cell Biology and The W. M. Keck Center for Computational Biology, Rice University

^* To whom correspondence should be addressed. Email: connell{at}acsu.buffalo.edu.

	Abstract

Colonization by Bordetella bronchiseptica elicits a variety of inflammatory respiratory infections including canine kennel cough, porcine atrophic rhinitis, and a whooping cough-like disease in humans. For successful colonization, B. bronchiseptica must acquire iron (Fe) from the infected host. A vast amount of Fe within the host is sequestered within heme, a metalloporphyrin which is coordinately bound in hemoglobin and myoglobin. Utilization of hemoglobin and myoglobin as sources of nutrient Fe by B. bronchiseptica requires expression of BhuR, an outer membrane protein. We hypothesize that hemin is acquired by B. bronchiseptica in a BhuR-dependent manner after spontaneous of the metalloporphyrin from hemoglobin and/or myoglobin. Sequestration experiments demonstrated that direct contact with hemoglobin or myoglobin was not required to support growth of B. bronchiseptica in an Fe-limiting environment. Mutant myoglobins, each exhibiting different affinities for heme, were employed to demonstrate that the rate of growth of B. bronchiseptica was directly correlated with the rate in which heme was lost from the hemoprotein. Finally, Escherichia coli cells expressing recombinant BhuR had the capacity to remove hemin from solution. Collectively, these experiments provided strong experimental support for the model that BhuR is a hemin receptor and that B. bronchiseptica likely acquires heme during infection after passive loss of the metalloporphyrin from hemoglobin and/or myoglobin. These results also suggest that spontaneous hemin loss by hemoglobin and myoglobin may be a common mechanism by which many pathogenic bacteria acquire heme and heme-bound Fe.