: The long-term goal of our research is to elucidate molecular mechanisms mediating host-microbe interactions and to learn how microbial processes affect the outcome of these relationships. The model bacterium we use for these studies is Xenorhabdus nematophila, which is both a mutualist (of nematodes) and a pathogen (of insects), and therefore an excellent model to understand both types of relationships. This proposal focuses on the mutualism between X. nematophila and the nematode and complements separately funded work in our lab on X. nematophila pathogenesis. Examining the mutualistic interactions of X. nematophila and its nematode host will expand our understanding of how animals evolve and maintain specific and dependent relationships with their micro-flora.
The specific aims of this proposal are geared toward genetically and biochemically characterizing several of the colonization initiation factors we have identified, as well as their interactions with each other.
Specific Aim 1 will test our hypotheses that membrane-localized colonization factors function in adherence to nematode cells, metal transport, and/or signal transduction. The results of these studies will elucidate the roles of Nil (nematode intestine localization) proteins in colonization events, shed light on the possible functions of Nil homologs of gram-negative pathogens in initiating infections, and further our understanding of molecular mechanisms mediating host-range specificity.
Specific Aim 2 is designed to dissect the functions of two regulators required for colonization, a sigma factor and a regulatory RNA. These experiments will yield insight into the signals perceived by X. nematophila during colonization, further define a colonization-specific regulon, and expand our knowledge of the role of a ubiquitous transcription factor in the natural ecology of a bacterium. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM059776-08
Application #
7058214
Study Section
Tropical Medicine and Parasitology Study Section (TMP)
Program Officer
Shapiro, Bert I
Project Start
1999-05-01
Project End
2008-04-30
Budget Start
2006-05-01
Budget End
2007-04-30
Support Year
8
Fiscal Year
2006
Total Cost
$329,023
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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