عنوان

Evolution of bacteriophages infecting Enterococcus from the human microbiome

Number

TL3dk3316p

.Language of Text, Soundtrack etc

انگلیسی

Title Proper

Evolution of bacteriophages infecting Enterococcus from the human microbiome

General Material Designation

[Thesis]

First Statement of Responsibility

Wandro, Stephen Joseph

Subsequent Statement of Responsibility

Whiteson, Katrine

Name of Publisher, Distributor, etc.

UC Irvine

Date of Publication, Distribution, etc.

2019

Body granting the degree

UC Irvine

Text preceding or following the note

2019

Text of Note

Enterococcus can be both a friend and a foe in the human microbiome. As an opportunistic pathogen, Enterococcus is normally benign. However, Enterococcus is responsible for many hospital-acquired infections and has shown rising rates of vancomycin resistance. Bacteriophages (phages) could be an alternative to antibiotics to target these antibiotic resistant bacteria, but the evolutionary and phenotypic outcomes of phage-bacteria interactions need to be investigated more thoroughly. We begin by investigating the gut microbiome of preterm infants that had been exposed to antibiotics to learn about the scenarios in which Enterococcus blooms occur in the gut (Chapter 1). We show that antibiotic exposed gut microbiomes are dominated by facultative anaerobes such as Enterococcus and Enterobacteriaceae. Further, we show that the bacterial composition is correlated to the overall metabolite profile. Metabolomics is a powerful tool for investigating microbial metabolism, and we contribute to the effort of developing standardized practices for metabolomics in the human microbiome by showing that freezing microbial samples required for long term storage (Chapter 2). Next, we investigated how phages could be used as therapeutics for treating Enterococcus blooms and infections (Chapters 3, 4, and 5). When Enterococcus is grown with its phages in vitro, it evolves resistance to phage infection by mutating exopolysaccharide synthesis genes. These mutations alter the exopolysaccharides on the surface of the bacterial cell to prevent binding of phage. Further, this mechanism of resistance appears to be a general mechanism leading to resistance against a diverse array of phages. This work demonstrates that experimental evolution is a powerful tool for characterizing interactions between bacteria and phages.Phage therapy is often administered as a cocktail of multiple phages, but there are no rules or best practices described for combining phages to be most effective. We show that in vitro, Enterococcus phage cocktails are more effective at preventing the growth of phage-resistant mutants, but the composition of the cocktail is important. Genetically diverse phage cocktails performed better than cocktails of related phages. My work demonstrates some of the outcomes of phage-Enterococcus interactions and will move us closer to applying phage therapy to treat Enterococcus infections.

Wandro, Stephen Joseph

Whiteson, Katrine

UC Irvine

Electronic name

p

[Thesis]

276903

a

Y