Loss of LasR function reshapes inter-species interactions in a polymicrobial cystic fibrosis airway model
type: CreativeWork
description: The airways of people with cystic fibrosis (CF) exhibit a particular predilection for infection by certain opportunistic pathogens. One such interloper is Pseudomonas aeruginosa, a WHO high-priority pathogen, infamous for its ability to evade antibiotic clearance. However, P. aeruginosa often has to share the airway environment with a variety of other microbes: these are polymicrobial infections. We now know that the interactions between co-habiting Gram-negative, Gram-positive, and fungal species can significantly impact the outcomes of these airway infections. Factors like intra-species genetic variation and (potentially existential) environmental challenges such as antibiotic treatment further complicate the situation. However, our understanding of the biology underpinning the microbial responses in such complex environments remains limited. In this study, I investigate the impact of loss-of-function of a gene (lasR) that is frequently mutated in CF isolates of P. aeruginosa, and also the impact of anti-pseudomonal drugs on a polymicrobial ecosystem populated by a representative selection of CF-associated microbes. To do this, I utilise an in vitro continuous-flow system that faithfully captures many of the microbial dynamics seen in CF patients. Using artificial sputum medium, this robust experimental platform enables the stable co-culture of P. aeruginosa alongside two other CF airway pathogens: Staphylococcus aureus and Candida albicans. I demonstrate that P. aeruginosa has the highest abundance in the studied polymicrobial community. Unexpectedly, the transcriptome of ‘wild-type’ P. aeruginosa was only minorly altered in the presence of other species, whereas the transcriptome of a lasR mutant showed substantial changes in the polymicrobial scenario. Furthermore, I found that the population dynamics of the lasR mutant, in co-culture with the ‘wild-type’, were very similar to those seen in people with CF (with the lasR mutant never exceeding ca. 10% of the ove…
abstract: The airways of people with cystic fibrosis (CF) exhibit a particular predilection for infection by certain opportunistic pathogens. One such interloper is Pseudomonas aeruginosa, a WHO high-priority pathogen, infamous for its ability to evade antibiotic clearance. However, P. aeruginosa often has to share the airway environment with a variety of other microbes: these are polymicrobial infections. We now know that the interactions between co-habiting Gram-negative, Gram-positive, and fungal species can significantly impact the outcomes of these airway infections. Factors like intra-species genetic variation and (potentially existential) environmental challenges such as antibiotic treatment further complicate the situation. However, our understanding of the biology underpinning the microbial responses in such complex environments remains limited. In this study, I investigate the impact of loss-of-function of a gene (lasR) that is frequently mutated in CF isolates of P. aeruginosa, and also the impact of anti-pseudomonal drugs on a polymicrobial ecosystem populated by a representative selection of CF-associated microbes. To do this, I utilise an in vitro continuous-flow system that faithfully captures many of the microbial dynamics seen in CF patients. Using artificial sputum medium, this robust experimental platform enables the stable co-culture of P. aeruginosa alongside two other CF airway pathogens: Staphylococcus aureus and Candida albicans. I demonstrate that P. aeruginosa has the highest abundance in the studied polymicrobial community. Unexpectedly, the transcriptome of ‘wild-type’ P. aeruginosa was only minorly altered in the presence of other species, whereas the transcriptome of a lasR mutant showed substantial changes in the polymicrobial scenario. Furthermore, I found that the population dynamics of the lasR mutant, in co-culture with the ‘wild-type’, were very similar to those seen in people with CF (with the lasR mutant never exceeding ca. 10% of the ove…
author: Bényei, Éva
language: eng
keywords: Cystic fibrosis, Polymicrobial, Pseudomonas aeruginosa, Staphylococcus aureus, Candida albicans, In vitro
license: https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/d254bb5b-69b3-4306-8145-c83cfe03837d/download
license: http://purl.org/NET/rdflicense/allrightsreserved
date published: 2024-10-25
date modified: 2026-07-22T22:24:31Z
provider: Cambridge University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Cambridge

PropertyValue
property ID: DOI
value: 10.17863/CAM.115544