In partial fulfillment of the requirements for the degree of 

Doctor of Philosophy in Biology

in the 

School of Biological Sciences

Angela Pena-Gonzalez

will defend her dissertation

INTEGRATING TRADITIONAL MICROBIOLOGY AND EPIDEMIOLOGY WITH CUTTING-EDGE (META-)GENOMICS TO IDENTIFY ENTERIC PATHOGENS AND ELUCIDATE THEIR SIGNATURES ON THE GUT MICROBIOME

Thursday, November 1st, 2018

2:00 PM

SEB Conference Room (122)

Thesis Advisor:

Dr. Kostas T. Konstantinidis

School of Civil and Environmental Engineering

Georgia Institute of Technology

Committee members: 

Dr. King Jordan

School of Biological Sciences

Georgia Institute of Technology

Dr. Frank Stewart

School of Biological Sciences

Georgia Institute of Technology

Dr. Gregory Gibson

School of Biological Sciences

Georgia Institute of Technology

Dr. Karen Levy

Rollin School of Public Health

Emory University

Summary

How enteric pathogens interact with the gut microbiome remains largely speculative; yet, this information is the cornerstone for better understanding the infection process and whether different pathogens, due to distinct virulence mechanisms, cause distinctive signatures in the microbiome. Such signatures could also be useful for diagnostics. Notably, a total of 38.4 million cases of foodborne illness per year cannot be attributed to specific causative agents, with diarrheal infections being predominant among them. Although most diarrheal cases quickly self-resolve and hence, do not require typing of the causative agent(s), there are instances where acute diarrheal infections could lead to mortality such as in children in the developing world, making detailed investigations of the causative agents and their signatures necessary. In this thesis, a new bioinformatics approach was devised that integrated traditional, culture-based information with epidemiologic data and metagenomic views of the gut microbiome in order to identify the causative agent of infectious diarrhea. Application to diarrhea samples from children in Ecuador (South America) and foodborne outbreaks in USA provided diagnostic signatures and signs of infection not attainable by traditional methods. For instance, our approach was able to distinguish pathogens from their innocuous, co-occurring commensal close relatives, and identified novel clonal complexes of E. coli-Shigella as the causative agents in about 50% of the diarrheal cases in Ecuador. The importance of these findings for diagnostics, and the risk from acquiring infection in rural vs. urban settings will be also discussed.