Beneficial microbes are essential for the overall health of eukaryotic organisms, including humans. To explore the fundamental principles underlying chronic infections of host epithelial tissue by beneficial microbes, I have been studying the mutualistic symbiosis between the marine bacterium Vibrio fischeri and the Hawaiian squid Euprymna scolopes. In particular, I have focused on characterizing the LuxU-LuxO signaling system of V. fischeri, which is conserved in all members of the Vibrionaceae, including pathogens such as V. cholerae and V. vulnificus. While this signaling system regulates virulence factors in pathogenic vibrios, my current research shows that LuxU-LuxO signaling is also important for V. fischeri to establish the symbiosis with squid. Recently, I have discovered that multiple sensor proteins interact with the LuxU-LuxO regulatory pathway, suggesting that a complex signaling network controls the expression of genes involved in bacterial colonization. Here, I propose to examine this form of signaling crosstalk as it functions in nature. Specifically, I plan to systematically characterize the interactions between LuxU and the sensor proteins using both genetic and biochemical approaches. I will also identify which sensor proteins are active in the host and determine their corresponding regulons. Finally, I will determine whether signaling by the LuxU-LuxO system has an impact on host mucus secretion, which terminates after V. fischeri successfully colonizes the squid. This K99 award will enable me to complete my postdoctoral training under the mentorships of Drs. Edward Ruby and Margaret McFall-Ngai, so I may launch a comprehensive interdisciplinary research program to study host-microbe interactions as an independent investigator at a major research institution.

Public Health Relevance

Bacteria must integrate multiple signaling inputs to coordinate responses appropriate to their environments. Examining cell signaling in a beneficial microbe within its natural host niche will uncover the fundamental principles of host-microbe interactions and contribute to our understanding of the roles microbes have on our health.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Transition Award (R00)
Project #
5R00GM097032-04
Application #
8642192
Study Section
Special Emphasis Panel (NSS)
Program Officer
Sledjeski, Darren D
Project Start
2011-06-01
Project End
2016-02-28
Budget Start
2014-03-01
Budget End
2015-02-28
Support Year
4
Fiscal Year
2014
Total Cost
$246,894
Indirect Cost
$75,928
Name
Pennsylvania State University
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
003403953
City
University Park
State
PA
Country
United States
Zip Code
16802
Verma, Subhash C; Miyashiro, Tim (2013) Quorum sensing in the squid-Vibrio symbiosis. Int J Mol Sci 14:16386-401
Sun, Yan; Bernardy, Eryn E; Hammer, Brian K et al. (2013) Competence and natural transformation in vibrios. Mol Microbiol 89:583-95