This proposal is aimed at understanding how bacteria interact with their eukaryotic hosts and how the availability of nutrients affects these interactions. The bacterium Xenorhabdus nematophilus provides a valuable model system of host microbe interactions: it is a symbiont that resides in the intestine of the nematode Steinernema carpocapsae and a pathogen that kills larval stage insects. The goals of this research are to identify the molecular mechanisms used by X. nematophilus to mediate host interactions. Nutrient deprivation in many Gram-negative bacteria triggers development of increased resistance to stress and the production of virulence determinants. This response is partially regulated by a specific sigma factor, ss. The first specific aim of this proposal is to analyze the role of ss and ss-dependent gene expression in the symbiosis and pathogenicity of X. nematophilus with its eukaryotic hosts. The results of this work will begin to address the genetic regulation of survival and adaptation in X. nematophilus and will provide insight into how the availability of nutrients affects host-bacterium interactions. X. nematophilus is likely to have evolved multiple regulatory mechanisms, including the starvation response, that mediate host interactions.
While specific Aim 1 focuses entirely on the starvation response, the goal of Specific Aim 2 is to perform genetic tests to identify additional bacterial regulatory mechanisms that mediate symbiosis between X. nematophilus and the nematode. The goal is to obtain and characterize X. nematophilus mutants that are no longer retained within the intestinal vesicles of nematodes. This work will provide insight into the genes and gene products that are essential for symbiosis and will aid in the elucidation of the regulation of host interactions in X. nematophilus and other bacteria.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM059776-03
Application #
6386576
Study Section
Special Emphasis Panel (ZRG1-TMP (01))
Program Officer
Shapiro, Bert I
Project Start
1999-05-01
Project End
2004-04-30
Budget Start
2001-05-01
Budget End
2002-04-30
Support Year
3
Fiscal Year
2001
Total Cost
$243,701
Indirect Cost
Name
University of Wisconsin Madison
Department
Microbiology/Immun/Virology
Type
Schools of Earth Sciences/Natur
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Veesenmeyer, Jeff L; Andersen, Aaron W; Lu, Xiaojun et al. (2014) NilD CRISPR RNA contributes to Xenorhabdus nematophila colonization of symbiotic host nematodes. Mol Microbiol 93:1026-42
Bhasin, Archna; Chaston, John M; Goodrich-Blair, Heidi (2012) Mutational analyses reveal overall topology and functional regions of NilB, a bacterial outer membrane protein required for host association in a model of animal-microbe mutualism. J Bacteriol 194:1763-76
Sugar, Darby R; Murfin, Kristen E; Chaston, John M et al. (2012) Phenotypic variation and host interactions of Xenorhabdus bovienii SS-2004, the entomopathogenic symbiont of Steinernema jollieti nematodes. Environ Microbiol 14:924-39
Chaston, John; Goodrich-Blair, Heidi (2010) Common trends in mutualism revealed by model associations between invertebrates and bacteria. FEMS Microbiol Rev 34:41-58
Richards, Gregory R; Goodrich-Blair, Heidi (2010) Examination of Xenorhabdus nematophila lipases in pathogenic and mutualistic host interactions reveals a role for xlpA in nematode progeny production. Appl Environ Microbiol 76:221-9
Herbert Tran, Erin E; Goodrich-Blair, Heidi (2009) CpxRA contributes to Xenorhabdus nematophila virulence through regulation of lrhA and modulation of insect immunity. Appl Environ Microbiol 75:3998-4006
Richards, Gregory R; Vivas, Eugenio I; Andersen, Aaron W et al. (2009) Isolation and characterization of Xenorhabdus nematophila transposon insertion mutants defective in lipase activity against Tween. J Bacteriol 191:5325-31
Richards, Gregory R; Goodrich-Blair, Heidi (2009) Masters of conquest and pillage: Xenorhabdus nematophila global regulators control transitions from virulence to nutrient acquisition. Cell Microbiol 11:1025-33
Herbert Tran, Erin E; Andersen, Aaron W; Goodrich-Blair, Heidi (2009) CpxRA influences Xenorhabdus nematophila colonization initiation and outgrowth in Steinernema carpocapsae nematodes through regulation of the nil locus. Appl Environ Microbiol 75:4007-14
Richards, Gregory R; Herbert, Erin E; Park, Youngjin et al. (2008) Xenorhabdus nematophila lrhA is necessary for motility, lipase activity, toxin expression, and virulence in Manduca sexta insects. J Bacteriol 190:4870-9

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