Degree Type

Dissertation

Date of Award

2018

Degree Name

Doctor of Philosophy

Department

Veterinary Microbiology and Preventive Medicine

Major

Microbiology

First Advisor

Catherine M. Logue

Second Advisor

Qijing Zhang

Abstract

Extraintestinal Pathogenic Escherichia coli (ExPEC) are a group of E. coli associated with disease outside the intestinal tract of the host. These organisms are known to cause a diversity of disease states in humans and animals. ExPEC are often divided into subpathotypes including Neonatal Meningitis E. coli (NMEC), associated with neonatal bacterial meningitis (NBM) in humans; uropathogenic E. coli (UPEC), associated with urinary tract infections in both humans and animals; and Avian Pathogenic E. coli (APEC), which causes colibacillosis in poultry. However, in vivo studies have demonstrated that the subpathotypes are more fluid than their names recognize. This work compares ExPEC subpathotypes to assess phenotypic and genomic differences amongst them. Specifically, differences between the subpathotypes are assessed via a phenotypic biofilm assay and polymorphisms in a known virulence factor, outer membrane protein A (OmpA). The results indicate that statistically significant similarities and differences were found between subpathotypes in their polymorphisms of OmpA and ability to form biofilms in certain media. Statistically significant differences were observed when the chromosomal differences of these E. coli are assessed via Clermont’s phylogenetic typing scheme. Both OmpA polymorphisms and biofilm formation results suggest that the phylogenetic groups are important when attempting to make generalizations about ExPEC subpathotypes. To examine an ExPEC subpathotype in greater resolution than traditional typing schemes allow, NMEC was chosen for a large sequencing study as NBM is a devastating disease that affects newborns resulting in sepsis and meningitis and mortality rate ranging from 15-40%. An examination of 58 NMEC genomic sequences found that NMEC had no conserved chromosomal type, as indicated via their serogroups, sequence types, phylogenetic groups, or identification of four NMEC clades based on the presence of conserved genes for each clade. Nineteen completed or nearly completed NMEC chromosomes concurred with this conclusion. An examination of NMEC plasmids revealed significant diversity among the Inc replicon types including the presence of Col replicons, yet IncFIB replicons were prevalent in most NMEC genomes. The NMEC sequencing data suggests that the NMEC subpathotype has considerable variation and that no strain should be considered prototypical.

Copyright Owner

Daniel Ward Nielsen

Language

en

File Format

application/pdf

File Size

204 pages

Available for download on Wednesday, November 18, 2020

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