Ongoing projects in the Ciofu Group

Project 1. The in vivo resistome of pathogenic biofilms

We propose the investigation of the “biofilm resistome”in in vivo experimental evolution studies in animal models of chronic P. aeruginosa infections under treatment with antimicrobials. Investigation of the infecting biofilm population at different time points during evolution by  phenotypic, genomic  and transcriptomic studies will allow identification of  general and antibiotic-specific evolutionary pathways leading to persistance of biofilm infections. This will enable intervention studies with anti-evolutionary compounds that prevent AMR development, such as anti-oxidants.

Project 2. The influence of the host immunity on the evolution  in biofilms

We propose to investigate the evolution of P. aeruginosa biofilm infections established in immunocompetent and immunodeficient animals as well as in animals with different levels of oxidative stress (guinea pigs model) under different antibiotic treatment conditions. These models of in vivo evolution will enable the investigation of immunomodulatory strategies on the development of AMR in biofilm infections.

Project 3. Control of pathogenic biofilms by bacteriophage-antibiotic combinations

Bacteriophages (i.e. viruses that infect bacteria) are promising alternatives to antibiotics in the prevention and treatment of Pseudomonas aeruginosa biofilm  infections.

The hypothesis is that phage/antibiotic exposure selects for strain-specific bacterial defence mechanisms in  P. aeruginosa (e.g. mutations, prophages, CRISPR) that can be used to predict the efficacy of the treatment and to guide phage/antibiotic therapy.

We propose to quantify strain-specific differences in the efficiency of phage/antibiotic combinations for controlling P. aeruginosa biofilms and to identify the underlying genetic mechanisms.This knowledge will enable the design of efficient strain-specific phage/antibiotic combinations against P. aeruginosa biofilm infections.