title: Albumin, in the Presence of Calcium, Elicits a Massive Increase in Extracellular Bordetella Adenylate Cyclase Toxin.
abstract: Pertussis (whooping cough), caused byBordetella pertussis, is resurging in the United States and worldwide. Adenylate cyclase toxin (ACT) is a critical factor in establishing infection withB. pertussisand acts by specifically inhibiting the response of myeloid leukocytes to the pathogen. We report here that serum components, as discovered during growth in fetal bovine serum (FBS), elicit a robust increase in the amount of ACT, and ≥90% of this ACT is localized to the supernatant, unlike growth without FBS, in which ≥90% is associated with the bacterium. We have found that albumin, in the presence of physiological concentrations of calcium, acts specifically to enhance the amount of ACT and its localization to the supernatant. Respiratory secretions, which contain albumin, promote an increase in amount and localization of active ACT that is comparable to that elicited by serum and albumin. The response to albumin is not mediated through regulation of ACT at the transcriptional level or activation of the Bvg two-component system. As further illustration of the specificity of this phenomenon, serum collected from mice that lack albumin does not stimulate an increase in ACT. These data, demonstrating that albumin and calcium act synergistically in the host environment to increase production and release of ACT, strongly suggest that this phenomenon reflects a novel host-pathogen interaction that is central to infection withB. pertussisand otherBordetellaspecies.
authors.affiliation: Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia, Charlottesville, Virginia, USA.
authors.forename: Laura A
authors.initials: LA
authors.lastname: Gonyar
authors.affiliation: Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia, Charlottesville, Virginia, USA.
authors.forename: Mary C
authors.initials: MC
authors.lastname: Gray
authors.affiliation: The Jackson Laboratory, Bar Harbor, Maine, USA.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Christianson
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Virginia, Charlottesville, Virginia, USA.
authors.forename: Borna
authors.initials: B
authors.lastname: Mehrad
authors.affiliation: Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia, Charlottesville, Virginia, USA EH2V@hscmail.mcc.virginia.edu.
authors.forename: Erik L
authors.initials: EL
authors.lastname: Hewlett
mesh_terms: D037361:Adenylate Cyclase Toxin / Q000097:blood*; D000418:Albumins / Q000737:chemistry*; D000818:Animals; D001886:Bordetella pertussis / Q000201:enzymology / Q000472:pathogenicity*; D018893:Bronchoalveolar Lavage; D002118:Calcium / Q000737:chemistry*; D002460:Cell Line; D054884:Host-Pathogen Interactions; D006801:Humans; D007962:Leukocytes / Q000276:immunology; D051379:Mice; D014917:Whooping Cough / Q000382:microbiology*
chemical_list: D037361:Adenylate Cyclase Toxin; D000418:Albumins; D002118:Calcium
keywords: Bordetella pertussis; RTX toxins; adenylate cyclase toxin; albumin; calcium