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 a variety of iron transport systems have been identified in Shigella and pathogenic E. coli, the sources of iron used by the pathogens when growing within the host and the specific iron transport systems involved in growth and survival in vivo are not known. Shigella species, the causative agents of dysentery, are closely related to E. coli and share many of the same iron transport systems. However, differences have been noted among this group of pathogens and those differences may relate to differences in sources of iron at various sites within the host or in the environment. Because Shigella spp. have the ability to invade host cells and grow with the cytosol, there may be specific iron transport systems associated with iron acquisition in the intracellular environment. Our first specific aim is to complete the characterization of the Shigella heme transport systems. Many shigellae and pathogenic E. coli, including O157:H7, have specific receptors for heme. Although receptors and other proteins involved in transporting heme across the bacterial cell wall have been identified, other steps in heme acquisition and its use as an iron source are not understood.
The second aim i s to use genetic and genomic approaches to identify the additional iron uptake systems in these pathogens. We will then apply these data and use the mutants created in these studies to help understand the role of the iron transport systems in growth and survival in vivo and in the environment. Thus our third specific aim is to determine which systems are used under specific environmental conditions and during intracellular growth. Our fourth specific aim is to assess expression of iron transport and other genes during intracellular growth and during infection by using microarray technology.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
2R37AI016935-19
Application #
6610144
Study Section
Special Emphasis Panel (ZRG1-BM-1 (02))
Program Officer
Hall, Robert H
Project Start
1980-09-30
Project End
2007-11-30
Budget Start
2003-06-15
Budget End
2003-11-30
Support Year
19
Fiscal Year
2003
Total Cost
$147,500
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
Koestler, Benjamin J; Ward, Cara M; Payne, Shelley M (2018) Shigella Pathogenesis Modeling with Tissue Culture Assays. Curr Protoc Microbiol 50:e57
Koestler, Benjamin J; Fisher, Carolyn R; Payne, Shelley M (2018) Formate Promotes Shigella Intercellular Spread and Virulence Gene Expression. MBio 9:
Rossi, Rachael M; Yum, Lauren; Agaisse, Hervé et al. (2017) Cardiolipin Synthesis and Outer Membrane Localization Are Required for Shigella flexneri Virulence. MBio 8:
Carpenter, Chandra; Payne, Shelley M (2014) Regulation of iron transport systems in Enterobacteriaceae in response to oxygen and iron availability. J Inorg Biochem 133:110-7
Carpenter, Chandra D; Cooley, Benjamin J; Needham, Brittany D et al. (2014) The Vps/VacJ ABC transporter is required for intercellular spread of Shigella flexneri. Infect Immun 82:660-9
Marman, Hannah E; Mey, Alexandra R; Payne, Shelley M (2014) Elongation factor P and modifying enzyme PoxA are necessary for virulence of Shigella flexneri. Infect Immun 82:3612-21
Pieper, Rembert; Fisher, C R; Suh, Moo-Jin et al. (2013) Analysis of the proteome of intracellular Shigella flexneri reveals pathways important for intracellular growth. Infect Immun 81:4635-48
Ma, Li; Payne, Shelley M (2012) AhpC is required for optimal production of enterobactin by Escherichia coli. J Bacteriol 194:6748-57
Broach, William H; Egan, Nicholas; Wing, Helen J et al. (2012) VirF-independent regulation of Shigella virB transcription is mediated by the small RNA RyhB. PLoS One 7:e38592
Be'er, Avraham; Florin, E-L; Fisher, Carolyn R et al. (2011) Surviving bacterial sibling rivalry: inducible and reversible phenotypic switching in Paenibacillus dendritiformis. MBio 2:e00069-11

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