Our research focuses on host responses to interactions with beneficial microbes. Within this context, the studies of my laboratory address five major questions:
- How are environmentally rare bacteria harvested from the host’s habitat during the onset of a horizontally transmitted symbiosis?
- By what mechanisms does the host recognize its specific symbiotic partner(s)?
- What are the influences of symbiotic bacteria on the developmental of the host tissues with which they associate?
- How is the symbiont population maintained in balance over the host’s lifetime, such that neither does the symbiont overgrow the host nor does the host eliminate the symbiont?
- What are the similarities and differences between pathogenic and beneficial animal-bacterial interactions?
- We have described the mechanism by which the newly hatched host enriches for V. fischeri, which accounts for less than 0.1% of the bacteria in the surrounding seawater. Non-specific, environmental peptidoglycan (a cell surface component of all bacteria) induces the host to shed mucus from an epithelial field near the site of colonization. V. fischeri specifically aggregates in this mucus for several hours and then invades host tissues.
- We have found that specificity begins outside the sites of eventual colonization, i.e., in the host-shed mucus. Further specificity determinants include: the provision of high levels of nitric oxide, a toxic oxygen species, in the ducts through which symbionts must migrate to colonize host crypt spaces; mannose-glycan interactions between the symbiont surfaces and host crypt epithelial cells.
- We have documented that V. fischeri induces profound developmental effects on the host light organ tissues, including apoptosis, macrophage-infiltration, cell swelling, increase in microvillar density, and a total remodeling of light organ morphology. Much of this development is mediated through bacterial factors, most commonly known as ‘microbe associated molecular patterns’ or ‘MAMPs’. Specifically, components of symbiont surface molecules, lipopolysaccharide and peptidoglycan, interact with host crypt epithelial to induce developmental pathways. The specific peptidoglycan fragment was identified as ‘tracheal cytotoxin’ or TCT, a molecule that has thus far only been reported to be exported by two pathogens, Neisseria gonorrheae and Bordetella pertussis.
- We have found that the symbiosis is controlled by a dramatic diel rhythm. Each day at dawn, the host vents 90-95% of its symbiont culture into the surrounding environment. Coupled with this rhythm is a marked remodeling of the crypt tissues. After venting, the tissues organize into highly polarized epithelia with dense lobate microvillar surfaces. With progression over the day, the tissues begin to take on a stressed appearance, with effacement of the epithelia and blebbing of the apical surfaces of the epithelial cells. Just before venting, the tissue is highly disorganized.
- The finding that ‘MAMPs’ mediate harvesting and much of development in the squid-vibrio system suggests that, at least in this system, beneficial and pathogenic bacteria are likely to use a similar molecular language to foster interaction.