Most bacterial pathogens have an absolute requirement for iron. The low availability of iron in most environments has led to the evolution of high affinity iron transport systems. Although iron acquisition systems have been identified in several gram negative organisms, the sources of iron used and the relative contribution of the different systems in their growth and survival in the host and in different niches in the external environment are not understood. Vibrio cholerae, the causative agent of cholera, is responsible for considerable morbidity and mortality worldwide. This organism is amenable to genetic manipulation, and several iron acquisition systems have already been identified. However, genetic analysis indicates that there are additional high-affinity iron transport systems in V. cholerae. The recent completion of its genome sequence will allow us to identify the remaining iron acquisition systems and to rigorously examine the roles of the systems in different environments and during exposure to different environmental stresses. Our first Specific Aim is to complete our characterization of V. cholerae heme transport and utilization. Our genetic data indicate that this pathogen expresses multiple heme transport systems, and we will define which genes are required for heme transport. We will also continue characterization of genes that function in the utilization of heme after it has been transported into the cell. Our second Specific Aim is to identify the transport systems used for the uptake of two exogenous siderophores used by V. cholerae, enterobactin and schizokinen. The third Specific Aim is to use our mutant collection, together with other reagents, to determine which transport systems are used during specific environmental conditions, and during growth in the vertebrate host.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI050669-04
Application #
6841166
Study Section
Bacteriology and Mycology Subcommittee 2 (BM)
Program Officer
Hall, Robert H
Project Start
2002-01-15
Project End
2006-12-31
Budget Start
2005-01-01
Budget End
2005-12-31
Support Year
4
Fiscal Year
2005
Total Cost
$300,000
Indirect Cost
Name
University of Texas Austin
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
170230239
City
Austin
State
TX
Country
United States
Zip Code
78712
Mey, Alexandra R; Butz, Heidi A; Payne, Shelley M (2015) Vibrio cholerae CsrA Regulates ToxR Levels in Response to Amino Acids and Is Essential for Virulence. MBio 6:e01064
Weaver, Emily A; Wyckoff, Elizabeth E; Mey, Alexandra R et al. (2013) FeoA and FeoC are essential components of the Vibrio cholerae ferrous iron uptake system, and FeoC interacts with FeoB. J Bacteriol 195:4826-35
Mey, Alexandra R; Craig, Stephanie A; Payne, Shelley M (2012) Effects of amino acid supplementation on porin expression and ToxR levels in Vibrio cholerae. Infect Immun 80:518-28
Wyckoff, Elizabeth E; Payne, Shelley M (2011) The Vibrio cholerae VctPDGC system transports catechol siderophores and a siderophore-free iron ligand. Mol Microbiol 81:1446-58
Be'er, Avraham; Ariel, Gil; Kalisman, Oren et al. (2010) Lethal protein produced in response to competition between sibling bacterial colonies. Proc Natl Acad Sci U S A 107:6258-63
Roux, Agnès; Payne, Shelley M; Gilmore, Michael S (2009) Microbial telesensing: probing the environment for friends, foes, and food. Cell Host Microbe 6:115-24
Wyckoff, Elizabeth E; Mey, Alexandra R; Payne, Shelley M (2007) Iron acquisition in Vibrio cholerae. Biometals 20:405-16
Wyckoff, Elizabeth E; Mey, Alexandra R; Leimbach, Andreas et al. (2006) Characterization of ferric and ferrous iron transport systems in Vibrio cholerae. J Bacteriol 188:6515-23
Mey, Alexandra R; Wyckoff, Elizabeth E; Kanukurthy, Vanamala et al. (2005) Iron and fur regulation in Vibrio cholerae and the role of fur in virulence. Infect Immun 73:8167-78
Mey, Alexandra R; Craig, Stephanie A; Payne, Shelley M (2005) Characterization of Vibrio cholerae RyhB: the RyhB regulon and role of ryhB in biofilm formation. Infect Immun 73:5706-19

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