FABICH RESEARCH GROUP
High Definition Microbial Bullying
While E. coli is less than 1% of the intestinal microbiome, it colonizes every mammal on the planet. During colonization, commensal and pathogenic E. coli use different nutrients and adapt to the dynamic mucus layer. Our group focuses on understanding how commensal E. coli interacts with the host to promote health as well as how pathogenic E. coli overcomes colonization resistance. Current lab members work on one of two projects: promoting health or causing disease.
During my time at The Ohio State University, I earned a B.S. in Molecular Genetics and did research in a cancer research lab. My undergraduate PI was the department chair and I was mentored by a post-doc at the bench. The project I worked on dealt with understanding protein-protein interactions regulating expression of the gene thymidylate synthase. The opportunities in the lab were unparalleled, except with the opportunities to take graduate level coursework during my last two years as an undergraduate. The heavy emphasis on eukaryotic systems left me wondering about our microbiome. In particular, I wanted to learn high-throughput approaches to answer questions about how E. coli colonizes the intestine.
My graduate degree (PhD) was from the University of Oklahoma in Microbiology. I was able to combine genome sequencing, gene chips, phenotype microarrays, tissue culture, and mutant construction to address colonization of the mouse intestine. I learned that while the good and bad E. coli compete for some identical nutrients, there were some unique nutrients used by each strain. One idea as to why they used different nutrients was that the pathogenic E. coli O157:H7 attached to the intestinal epithelium as a unique nutrient-niche. However, combination of up to seven adhesin mutants (intimin, tir, espA, F9, ompA, paa, ecpA, and lpfAE) in one strain was able to co-colonize the intestine. Since attachment was a non-issue for colonization, I characterized a laboratory strain that colonized better. I sequenced its genome and combined it with several high-throughput approaches to determine that flhDC primarily governs carbon catabolism and energy metabolism to outcompete its wild-type.
Recently, my lab sequenced the common strain used to model E. coli O157:H7.
Citrobacter rodentium strain DBS100 is the model organism to study EHEC pathogenesis in mice. The goal is to focus on the same adhesins as O157:H7 in addition to determining that attachment is primarily for pathogenesis. During colonization of the continuous streptomycin-treated mouse model, C. rodentium colonizes without causing disease. We seek to understand the molecular signals with the host and the microbiome.
Currently, we are also focusing on what causes the intestinal adaptation of commensal E. coli.
To do this, we have begun our analysis in looking at what regulates flhDC. The first flhDC regulator we have looked at is qseC, which is involved in quorum sensing. We have found that the quorum sensing hinders colonization and is related to lag. The work is being submitted for publication and will redefine regulation of the lac operon.
The intersection of health and disease
MICROBIOMICS OF PATHOGENIC ECOLOGY
Historically, we have emphasized what makes us sick. Only now are we realizing that what keeps us healthy is just as important. Our research aims to understand the intersection between gastrointestinal health and disease.