The long-term objectives of the proposed research are to understand the complex dialogue that occurs between humans and their microbiota during the initial minutes to hours of their interaction. These relationships, whether pathogenic or beneficial, typically begin at mucosal surfaces, sites that are often inaccessible to experimental study. In addition, they usual support a complex consortium consisting of hundreds of microbial species. At these sites, the interplay between the surface features of bacteria and the corresponding mechanisms of host recognition controls the initiation and persistence of both beneficial and pathogenic associations. How is this same cellular and molecular 'language'used differently to produce the two opposite outcomes of health or disease? To answer this question in the face of the daunting microbial complexity in the human body, simpler model systems are used that are more amenable to experimental manipulation. Biologists use such systems to discover fundamental principles that reveal how an individual bacterial species associates successfully with its host. One such model is the binary symbiosis between the bioluminescent Gram-negative bacterium, Vibrio fischeri, and its squid host, Euprymna scolopes. As in humans, the squid's relationship with this bacterium begins a new each generation, with the microbe transitioning from the environment into a functional beneficial relationship. In both cases, a 'winnowing'occurs that promotes an association with only that small subset of environmental bacteria that are recognized through complex molecular interactions. In the squid-vibrio system, this process occurs over minutes to hours, and can be directly imaged in its entirety. As such, the system offers the rare opportunity to decipher, with high temporal and spatial resolution, the reciprocal molecular and biochemical dialogue that is essential for a natural association to develop normally. This project brings together a team of scientists with expertise in cell and developmental biology, biochemistry, and genetics, to address the following specific aims: 1) to examine how interactions between host cells and the specific symbiont shape the microenvironment to promote partner recognition and specificity;2) to characterize the genetic factors of the symbiont that are essential to the selection process;and, 3) to define how bacterial motility and outer membrane vesicles, well known virulence and colonization determinants, play a key role in the dialogue between host and symbiont.

Public Health Relevance

A critical period in the colonization of humans and other animals by both the normal microbiota and encroaching microbial pathogens is the very first minutes to hours of their encounter with host cells. The interplay between the two partners at this juncture determines whether a healthy association will be fostered, a dysfunctional microbial community will develop, or a frank pathogenesis will ensue. A collaborative team of scientists, using a combination of host cell biology and microbial genetics, will discover the molecular and biochemical underpinnings of this crucial period, defining the general principles that govern the reciprocal interactions between host cells and the microbes in their environment.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
2R01AI050661-11A1
Application #
8486756
Study Section
Host Interactions with Bacterial Pathogens Study Section (HIBP)
Program Officer
Hall, Robert H
Project Start
2001-12-01
Project End
2017-05-31
Budget Start
2013-06-01
Budget End
2014-05-31
Support Year
11
Fiscal Year
2013
Total Cost
$437,722
Indirect Cost
$139,018
Name
University of Wisconsin Madison
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Aschtgen, Marie-Stephanie; Lynch, Jonathan B; Koch, Eric et al. (2016) Rotation of Vibrio fischeri Flagella Produces Outer Membrane Vesicles That Induce Host Development. J Bacteriol 198:2156-65
Schwartzman, Julia A; Ruby, Edward G (2016) A conserved chemical dialog of mutualism: lessons from squid and vibrio. Microbes Infect 18:1-10
Bongrand, Clotilde; Koch, Eric J; Moriano-Gutierrez, Silvia et al. (2016) A genomic comparison of 13 symbiotic Vibrio fischeri isolates from the perspective of their host source and colonization behavior. ISME J 10:2907-2917
Aschtgen, Marie-Stephanie; Wetzel, Keith; Goldman, William et al. (2016) Vibrio fischeri-derived outer membrane vesicles trigger host development. Cell Microbiol 18:488-99
Schwartzman, Julia A; Ruby, Edward G (2016) Stress as a Normal Cue in the Symbiotic Environment. Trends Microbiol 24:414-24
Nikolakakis, K; Monfils, K; Moriano-Gutierrez, S et al. (2015) Characterization of the Vibrio fischeri Fatty Acid Chemoreceptors, VfcB and VfcB2. Appl Environ Microbiol 82:696-704
Krasity, Benjamin C; Troll, Joshua V; Lehnert, Erik M et al. (2015) Structural and functional features of a developmentally regulated lipopolysaccharide-binding protein. MBio 6:e01193-15
Nikolakakis, K; Lehnert, E; McFall-Ngai, M J et al. (2015) Use of Hybridization Chain Reaction-Fluorescent In Situ Hybridization To Track Gene Expression by Both Partners during Initiation of Symbiosis. Appl Environ Microbiol 81:4728-35
Schwartzman, Julia A; Koch, Eric; Heath-Heckman, Elizabeth A C et al. (2015) The chemistry of negotiation: rhythmic, glycan-driven acidification in a symbiotic conversation. Proc Natl Acad Sci U S A 112:566-71
Pan, Min; Schwartzman, Julia A; Dunn, Anne K et al. (2015) A Single Host-Derived Glycan Impacts Key Regulatory Nodes of Symbiont Metabolism in a Coevolved Mutualism. MBio 6:e00811

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