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Slideshow

Ottesen

 

Work in the Ottesen lab seeks to understand the structure and function of complex microbial communities, and the ways in which microbes interact with and perceive complex environments.  A major focus is the use of molecular ecological tools to observe microbial behavior in the environment.  This includes not only observing and tracking changes in which microbes are present in an environment, but also using community transcriptomics to observe changes in microbial gene expression over time.  By studying microbial behavior “in the wild”, we hope to gain a better understanding of the roles and significance of diverse members of the uncultured microbial majority. 

 

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Host and microbial contributions to microbiome stability and dynamics

 

We (and most other higher organisms) are hosts to complex gut microbial communities that aid in digestion and help shape our overall health.  We are using the American cockroach (Periplaneta americana) and its gut microbiome as a model system to understand gut microbiome stability and dynamics, particularly responses to dietary perturbation. We use the cockroach as a model host organism because they are robust, low-maintenance insects that reproduce quickly, eat a diverse, omnivorous diet, and their digestive tract hosts a highly diverse gut microbiome dominated by bacterial families found in the guts of many other animals, including mammals and humans. 

 

A key observation underlying our work in the cockroach is that the taxonomic composition of their gut microbiome is exceptionally stable following major dietary shifts.  We have since compiled genomic, metagenomic, and metatranscriptomic data showing that this is not due to an unusual distribution of metabolic roles among cockroach gut microbes, but is rather the result of a robust network of stabilizing interactions in the cockroach gut microbiome.  Analysis of gut metatranscriptomes suggests that fiber-degrading bacteria at the top of the gut 'food chain' are critical to this stability.  They respond to host diet shifts by utilizing whatever polysaccharides present in each diet or by breaking down host glycans under starvation conditions or in response to diets that lack polysaccharides.  This adaptation is sufficient to allow microbes that are 'lower' on the microbial food chain to maintain stable activity across diets.  Follow-up work has shown that synthetic diets containing high concentrations of single purified polysaccharide types can disrupt gut microbiome interaction networks, leading to blooms of specialized microbes and reduced gut microbiome stability.

 

We are now working to better understand microbial functional roles in the gut microbiota and the ways in which diverse microbial taxa contribute to gut microbiota stability.  We are also beginning new work examining how the host immune system and other host activities shape gut microbiome homeostasis.  Finally, we are using germ-free cockroaches to test hypotheses regarding the ways in which individual microbial interactions can shape gut microbiome composition and stability.

 


 

 

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Antibiotic resistance ecology and the movement of AR genes and pathogens across the landscape. 

A second project in the Ottesen laboratory grew out of our work on stream microbial communities.  While we were examining the microbiome of our local streams, we were surprised to find high numbers of antibiotic resistant bacteria and pathogens.  We have since followed up on this work to discover that antibiotic resistance is widespread in the greater Athens area, and is strongly linked to contamination with human fecal bacteria, suggesting that sewer leaks and failing septic systems may be responsible for much of the antibiotic resistance present in our watershed.

 

This work has caused us to become very interested in understanding antibiotic resistance in the human microbiome and how bacteria and antibiotic resistance genes move between humans and the environment.  A follow-up project showed persistent, asymptomatic carriage of antibiotic resistant E. coli in the guts of local residents, as well as horizontal transfer of AR genes between bacteria in the gut.

 

We are now seeking funding to follow up on this work with a population genomic analysis examining the movement of E. coli and antibiotic resistance genes between humans and the environment,  as well as a comparison of commensal and environmental E. coli with pathogenic isolates from human infections.

 

 

Jonathan Frye

Adjunct Research Microbiologist

Our laboratory investigates antibiotic resistance, pathogenicity, genomics, and the evolution of Salmonella enterica. Salmonella is one of the most prevalent foodborne pathogens globally and is estimated to cause over one million infections in the U.S. each year. Antimicrobial resistance is also common in Salmonella and has been increasing over the past few decades. We have pioneered the application of microarrays, next-generation sequencing, and other innovative methods for investigating Salmonella. These studies identified IncA/C and other plasmids that are responsible for much of the multi drug resistance (MDR) in Salmonella isolated from food animals. These plasmids are large (100-250kb), can encode resistance to twelve or more antimicrobials, and are self-transmissible. Our current studies have determined that the resistance genes found in Salmonella isolated from food animals, retail meats, and human infections are genetically similar indicating that some MDR Salmonella likely developed in animals and were transmitted to humans via food. New studies will test this hypothesis and identify points in food production where antimicrobial resistance develops that can be targeted to improve food safety.

Our laboratory’s genomic analysis projects identified genes found in different Salmonella serovars that are responsible for their variability in host range and pathogenicity. We developed assays based on these genetic differences to detect dangerous Salmonella serovars such as Heidelberg and Typhimurium in food. We have also used this data to develop an automated, high-throughput PCR and capillary analysis technique to identify the top 100 clinical Salmonella serotypes (SMART: Salmonella multiplex assay for rapid typing). Testing has shown that SMART is more accurate, easier, quicker, and cheaper than traditional serotyping. Our ongoing investigation of Salmonella genomics has completed the sequencing of 200 Salmonella genomes that represent the genetic diversity found in the most prevalent clinical Salmonella serovars. Our laboratory’s new studies use this database to improve our understanding of Salmonella evolution and enable us to identify genetic markers for pathogenicity, host range, and host specificity. These markers will be used to develop rapid methods for Salmonella outbreak investigations and improve our ability to protect human health. Recently we have expanded our work to address a major data gap by determining what role surface water plays in the development of antimicrobial resistance in bacteria and its spread to humans and animals. This work is a collaboration with Dr. Elizabeth Ottesen, Dr. Erin Lipp., and Dr. Charlene Jackson. Together we are working with the Upper Oconee River Watershed Network (UWON), a group of volunteers that do a quarterly evaluation of the surface waters that feed the Oconee River. We have been sampling the water with their help since Winter of 2015. While Dr. Ottesen focuses on the metagenome of the watershed and Dr. Lipp looks at the ecology of the watershed, Dr. Jackson and I are isolating bacteria, investigating their prevalence, antimicrobial resistance, and genotypes. Our current work is looking at Salmonella, Escherichia coli, and Enterococcus spp. Together we hope to get a comprehensive picture of what is in the watershed and how it changes over time.

Education:
  • Ph.D. in Microbiology, University of Georgia (2000)
  • B.S. in Biology, East Carolina University (1993)
Labs (via personnel):
Labs:

Mark A. Eiteman

Adjunct Professor
Education:

Undergrad:                  B.S., Chemical Engineering, Summa cum laude, Virginia Tech, 1986

Graduate work:           M.S., Chemical Engineering, University of Virginia, 1988

                                    Ph.D., Chemical Engineering, University of Virginia, 1991

Research Interests:

The research interests of Mark A. Eiteman are in fermentation and biotechnology with emphasis on microbial processes to generate fuels and chemicals. He has special interests in nutrient-limited processes, which can be used very effectively to drive a metabolic network toward a particular biochemical product.  Dr. Eiteman focuses on central metabolism and the effect of redox constraints:  genetic perturbations and operational conditions have a significant impact on the balance of NAD(P)H/NAD(P) available to direct central metabolites to the biochemical product of interest.  While much current research elsewhere typically focuses on synthetic biology at the small scale, Dr. Eiteman’s work additionally transitions small scale results into bioprocess operations, involving scale-up to a controlled bioreactor.  By working at the interface of synthetic biology and fermentation process design, Dr. Eiteman’s work uniquely allows process conditions to inform the desirable metabolic engineering strategy needed, and vice versa.  Recent work has included a variety of products from central metabolism such as citramalic acid, succinic acid, lactic acid, pyruvic acid and 5-aminolevulinic acid, as well as glycosylated small molecules and rare sugars.  Dr. Eiteman also has a continued interest in biological approaches to other problems, such as methods to convert effectively into products the sugar mixtures found in lignocellulosic hydrolysates, and the process of adaptive evolution.

Dr. Eiteman regularly teaches senior-level and graduate-level courses in biochemical engineering (ENGR4510/6510) and bioseparations (ENGR4520/6520).  Dr. Eiteman also serves as an instructor for Fermentation Engineering Laboratory (BCHE8210) presenting advanced fermentation principles coupled with design of experiments and interpretation of results.

Of note:

Editorial Board, Applied and Environmental Microbiology (2016-)

President, Institute of Biological Engineering (2019-2020)

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