Manganese transporters Yfe and MntH are Fur-regulated and important for the virulence of Yersinia pestis.
Yersinia pestis has a flea-mammal-flea transmission cycle, and is a zoonotic pathogen that causes the systemic diseases bubonic and septicaemic plague in rodents and humans, as well as pneumonic plague in humans and non-human primates. Bubonic and pneumonic plague are quite different diseases that result from different routes of infection. Manganese (Mn) acquisition is critical for the growth and pathogenesis of a number of bacteria. The Yfe/Sit and/or MntH systems are the two prominent Mn transporters in Gram-negative bacteria. Previously we showed that the Y. pestis Yfe system transports Fe and Mn. Here we demonstrate that a mutation in yfe or mntH did not significantly affect in vitro aerobic growth under Mn-deficient conditions. A yfe mntH double mutant did exhibit a moderate growth defect which was alleviated by supplementation with Mn. No short-term energy-dependent uptake of (54)Mn was observed in this double mutant. Like the yfeA promoter, the mntH promoter was repressed by both Mn and Fe via Fur. Sequences upstream of the Fur binding sequence in the yfeA promoter converted an iron-repressible promoter to one that is also repressed by Mn and Fe. To our knowledge, this is the first report identifying cis promoter elements needed to alter cation specificities involved in transcriptional repression. Finally, the Y. pestis yfe mntH double mutant had an ~133-fold loss of virulence in a mouse model of bubonic plague but no virulence loss in the pneumonic plague model. This suggests that Mn availability, bacterial Mn requirements or Mn transporters used by Y. pestis are different in the lungs (pneumonic plague) compared with systemic disease.
Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky, Lexington, KY 40536-0298, USA.
Robert D
RD
Perry
Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky, Lexington, KY 40536-0298, USA.
Susannah K
SK
Craig
Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky, Lexington, KY 40536-0298, USA.
Jennifer
J
Abney
Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky, Lexington, KY 40536-0298, USA.
Alexander G
AG
Bobrov
Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky, Lexington, KY 40536-0298, USA.
Olga
O
Kirillina
Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky, Lexington, KY 40536-0298, USA.
Ildefonso
I
Mier
Department of Institutional Research Planning and Effectiveness, University of Kentucky, Lexington, KY 40536, USA.
Helena
H
Truszczynska
Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky, Lexington, KY 40536-0298, USA.
Jacqueline D
JD
Fetherston
D000818:Animals; D019677:Artificial Gene Fusion; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D017353:Gene Deletion; D015964:Gene Expression Regulation, Bacterial; D017930:Genes, Reporter; D006801:Humans; D008345:Manganese / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D010930:Plague / Q000382:microbiology / Q000473:pathology; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000378:metabolism*; D016019:Survival Analysis; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*; D015010:Yersinia pestis / Q000235:genetics / Q000254:growth & development / Q000378:metabolism* / Q000472:pathogenicity*; D001616:beta-Galactosidase / Q000032:analysis / Q000235:genetics
D001426:Bacterial Proteins; D027682:Cation Transport Proteins; D026901:Membrane Transport Proteins; C433793:MntH protein, bacteria; D012097:Repressor Proteins; D037521:Virulence Factors; C068477:ferric uptake regulating proteins, bacterial; D008345:Manganese; D001616:beta-Galactosidase