title: The Yersinia pestis siderophore, yersiniabactin, and the ZnuABC system both contribute to zinc acquisition and the development of lethal septicaemic plague in mice.
abstract: Bacterial pathogens must overcome host sequestration of zinc (Zn(2+) ), an essential micronutrient, during the infectious disease process. While the mechanisms to acquire chelated Zn(2+) by bacteria are largely undefined, many pathogens rely upon the ZnuABC family of ABC transporters. Here we show that in Yersinia pestis, irp2, a gene encoding the synthetase (HMWP2) for the siderophore yersiniabactin (Ybt) is required for growth under Zn(2+) -deficient conditions in a strain lacking ZnuABC. Moreover, growth stimulation with exogenous, purified apo-Ybt provides evidence that Ybt may serve as a zincophore for Zn(2+) acquisition. Studies with the Zn(2+) -dependent transcriptional reporter znuA::lacZ indicate that the ability to synthesize Ybt affects the levels of intracellular Zn(2+) . However, the outer membrane receptor Psn and TonB as well as the inner membrane (IM) ABC transporter YbtPQ, which are required for Fe(3+) acquisition by Ybt, are not needed for Ybt-dependent Zn(2+) uptake. In contrast, the predicted IM protein YbtX, a member of the Major Facilitator Superfamily, was essential for Ybt-dependent Zn(2+) uptake. Finally, we show that the ZnuABC system and the Ybt synthetase HMWP2, presumably by Ybt synthesis, both contribute to the development of a lethal infection in a septicaemic plague mouse model.
authors: Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky, Lexington, KY, USA.
authors: Alexander G
authors: AG
authors: Bobrov
authors: Olga
authors: O
authors: Kirillina
authors: Jacqueline D
authors: JD
authors: Fetherston
authors: M Clarke
authors: MC
authors: Miller
authors: Joseph A
authors: JA
authors: Burlison
authors: Robert D
authors: RD
authors: Perry
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000818:Animals; D004195:Disease Models, Animal; D051379:Mice; D010636:Phenols / Q000378:metabolism*; D010930:Plague / Q000382:microbiology* / Q000473:pathology; D018805:Sepsis / Q000382:microbiology / Q000473:pathology; D013844:Thiazoles / Q000378:metabolism*; D014774:Virulence; D037521:Virulence Factors / Q000378:metabolism*; D015010:Yersinia pestis / Q000378:metabolism*; D015032:Zinc / Q000378:metabolism*
chemical_list: D018528:ATP-Binding Cassette Transporters; D010636:Phenols; D013844:Thiazoles; D037521:Virulence Factors; C104398:yersiniabactin; D015032:Zinc