Evolutionary responses of microbiomes during therapeutic interventions

Lead Research Organisation: University of York
Department Name: Biology

Abstract

The rapid rise of antibiotic resistance has made many clinical antibiotics
ineffective. One way to increase the efficiency of antibiotics is to use them in
combination with bacteria-specific parasitic viruses, phages. Mechanistically, this
is thought to function due to collateral sensitivity where selection by one agent
makes the pathogen more susceptible to selection by the other. However, it is
unclear how phage-antibiotic synergies are realized in complex microbiomes, to
what extent pathogen resistance evolution is shaped by the presence of other
bacteria and how these evolutionary processes are affected by the spatial
structure of the physical environment typical for CF lungs.
Pseudomonas aeruginosa is a human opportunistic pathogen characterised by
high levels of antibiotic resistance. It is the main source of morbidity in Cystic
Fibrosis (CF) lung infections where it is typically embedded in spatially structured
polymicrobial communities. The proposed multidisciplinary PhD project will
develop novel phage-antibiotic combination therapies across a range of spatial
scales (microcosms vs. microfluidics) to control P. aeruginosa in polymicrobial CF
communities. The key aims include:
1) Studying the effectiveness of phage-antibiotic synergy across CF
community diversity gradient in terms of survival of the P. aeruginosa focal
pathogen
2) Quantifying the evolutionary responses of the P. aeruginosa focal
pathogen across the CF community diversity gradient (underlying genetic
changes)
3) Understanding the role of spatial structure for the success of therapeutic
interventions and the likelihood of focal pathogen resistance evolution
This project will combine evolutionary theory, microbial ecology, phage biology
and microfluidics. You will also have a possibility to sequence evolved pathogen
strains and develop bioinformatics and statistical analysis skills. An ideal
candidate will have a background in at least one of the main subject areas
(microbiology, community ecology, experimental evolution or phage biology) and
willingness to develop skills in the other areas.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/M011151/1 30/09/2015 29/09/2023
2280240 Studentship BB/M011151/1 30/09/2019 29/09/2023 Ezra Levi Herman