IRON ACQUISITION IN BORDETELLA PERTUSSIS

Summary

Principal Investigator: SANDRA KAY ARMSTRONG
Abstract: DESCRIPTION (provided by applicant): Bacterial growth in vivo is the primary requirement for pathogenicity, and growth is limited by nutrient availability, which can change during the course of an infection. Iron that is essential for virtually all bacterial growth is actively withheld by mammalian defense mechanisms. Bordetella pertussis and Bordetella bronchiseptica are highly genetically related bacterial species that cause respiratory infections in mammals. B. pertussis is the agent that colonizes the human respiratory epithelium to cause whooping cough, or pertussis, and B. bronchiseptica infects a wide range of nonhuman mammals. For iron retrieval, B. pertussis and B. bronchiseptica produce and utilize the siderophore alcaligin, and can also use the enterobactin siderophore and host heme compounds. Under iron starvation conditions in vitro and in vivo, each system is positively regulated by the action of a distinct transcriptional regulator. These regulators are activated by the cognate iron source acting as the inducer, allowing maximal expression of the genes required for its utilization. Previous studies showed that these iron acquisition systems are important for B. pertussis infection. They are differentially expressed in a host, and their expression patterns reflect changes in iron source availability during infection. The alcaligin system is important for B. pertussis growth during the entire infection, enterobactin utilization is most important to successful early infection and the heme system is required only at later stages of infection. Our long-term interests are to further our understanding of nutrient acquisition as a key virulence determinant in Bordetella species. The proposed research is focused on extending our knowledge of Bordetella iron assimilation to characterize newly identified iron transport systems and determine their importance to growth in the host. In this research, we will define the role of key Fbp system components in Bordetella utilization of ferric siderophores and characterize an apparently novel mechanism for utilization of ferrous iron. Lastly, we will investigate the means by which Bordetella cells use host neuroendocrine stress hormones to obtain the iron from transferrin and lactoferrin. PUBLIC HEALTH RELEVANCE: Nearly all bacteria require iron for growth and pathogenic bacteria must be able to obtain this essential nutrient in the iron-limiting host environment. Bordetella pertussis is the causative agent of whooping cough, or pertussis, in humans and the related Bordetella bronchiseptica causes respiratory infections in a variety of nonhuman mammals. These bacteria use multiple mechanisms to obtain iron in the host and mutants defective in those mechanisms have dramatically reduced virulence. Information obtained in these studies will define the mechanisms of iron uptake and characterize host factors that influence the ability of these pathogens to obtain iron. This increased understanding may lead to improved strategies to prevent growth of these, and other respiratory pathogens, in humans.
Funding Period: 1991-08-01 - 2014-12-31
more information: NIH RePORT

Top Publications

  1. pmc Norepinephrine mediates acquisition of transferrin-iron in Bordetella bronchiseptica
    Mark T Anderson
    Department of Microbiology, University of Minnesota, Minneapolis, MN 55455 0312, USA
    J Bacteriol 190:3940-7. 2008
  2. pmc Differential expression of Bordetella pertussis iron transport system genes during infection
    Timothy J Brickman
    Department of Microbiology, University of Minnesota Medical School, 925 Mayo Memorial Building, 420 Delaware Street, S E, Minneapolis, MN 55455 0312, USA
    Mol Microbiol 70:3-14. 2008
  3. pmc Temporal signaling and differential expression of Bordetella iron transport systems: the role of ferrimones and positive regulators
    Timothy J Brickman
    Department of Microbiology, University of Minnesota Medical School, MMC 196, Minneapolis, MN 55455 0312, USA
    Biometals 22:33-41. 2009
  4. pmc Transcriptional profiling of the iron starvation response in Bordetella pertussis provides new insights into siderophore utilization and virulence gene expression
    Timothy J Brickman
    Department of Microbiology, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA
    J Bacteriol 193:4798-812. 2011
  5. pmc Iron and pH-responsive FtrABCD ferrous iron utilization system of Bordetella species
    Timothy J Brickman
    Department of Microbiology, University of Minnesota Medical School, 925 Mayo Memorial Building, 420 Delaware Street, S E, Minneapolis, MN 55455 0312, USA
    Mol Microbiol 86:580-93. 2012
  6. pmc Role of Bordetella pertussis RseA in the cell envelope stress response and adenylate cyclase toxin release
    Tomoko Hanawa
    Department of Infectious Diseases, Kyorin University School of Medicine, Mitaka, Tokyo, Japan
    Pathog Dis . 2013

Research Grants

Detail Information

Publications6

  1. pmc Norepinephrine mediates acquisition of transferrin-iron in Bordetella bronchiseptica
    Mark T Anderson
    Department of Microbiology, University of Minnesota, Minneapolis, MN 55455 0312, USA
    J Bacteriol 190:3940-7. 2008
    ..bronchiseptica iron acquisition from the iron carrier protein transferrin and this process may represent a mechanism by which some bacterial pathogens obtain this essential nutrient in the host environment...
  2. pmc Differential expression of Bordetella pertussis iron transport system genes during infection
    Timothy J Brickman
    Department of Microbiology, University of Minnesota Medical School, 925 Mayo Memorial Building, 420 Delaware Street, S E, Minneapolis, MN 55455 0312, USA
    Mol Microbiol 70:3-14. 2008
    ..pertussis is iron-starved and responds to the presence of diverse iron sources during natural infection...
  3. pmc Temporal signaling and differential expression of Bordetella iron transport systems: the role of ferrimones and positive regulators
    Timothy J Brickman
    Department of Microbiology, University of Minnesota Medical School, MMC 196, Minneapolis, MN 55455 0312, USA
    Biometals 22:33-41. 2009
    ..As inducers, the iron sources function as chemical signals termed ferrimones. Ferrimone-sensing allows the pathogen to adapt and exploit early and late events in the infection process...
  4. pmc Transcriptional profiling of the iron starvation response in Bordetella pertussis provides new insights into siderophore utilization and virulence gene expression
    Timothy J Brickman
    Department of Microbiology, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA
    J Bacteriol 193:4798-812. 2011
    ..These results indicate that iron starvation in the infected host is an important environmental cue influencing not only Bordetella iron transport gene expression but also the expression of other important virulence-associated genes...
  5. pmc Iron and pH-responsive FtrABCD ferrous iron utilization system of Bordetella species
    Timothy J Brickman
    Department of Microbiology, University of Minnesota Medical School, 925 Mayo Memorial Building, 420 Delaware Street, S E, Minneapolis, MN 55455 0312, USA
    Mol Microbiol 86:580-93. 2012
    ..The pH of human airway surface fluids ranges from pH 5.5 to 7.9, and the FtrABCD system may supply ferrous iron necessary for Bordetella growth in acidic host microenvironments in which siderophores are ineffective for iron retrieval...
  6. pmc Role of Bordetella pertussis RseA in the cell envelope stress response and adenylate cyclase toxin release
    Tomoko Hanawa
    Department of Infectious Diseases, Kyorin University School of Medicine, Mitaka, Tokyo, Japan
    Pathog Dis . 2013
    ..Consistent with this, compared with the wild-type strain, rseA mutant cells produced increased numbers of large surface-associated vesicles...

Research Grants30

  1. Iron Acquisition by Mycobacterium tuberculosis Within Phagocytes
    Bradley E Britigan; Fiscal Year: 2013
    ..Thus, increased understanding of how M. tuberculosis acquires and uses Fe during infection could lead to the development of new antibiotics to be used in treating TB, something that would be of great benefit to veterans. ..
  2. Function and Secretion of Bordetella Filamentous Hemagglutinin
    Peggy A Cotter; Fiscal Year: 2013
    ..Our results will provide insight into the TPS mechanism, and may set a new paradigm for how proteins are folded on cell surfaces. ..