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Elucidating the mechanism of antimicrobial resistance in polymicrobial infections

Principal Supervisor: Dr. Rebecca A Hall, School of Biosciences

Co-supervisor: Dr Jessica Blair, Institute of Microbiology and Infection

PhD project title: Elucidating the mechanism of antimicrobial resistance in polymicrobial infections

University of Registration: University of Birmingham

Project outline:

Antimicrobial resistance is major public health concern. Antibiotic resistant bacterial infections currently kill 700,000 people annually and this figure is rising. Fungal pathogens kill more than 1.6 million people every year and are also becoming more resistant to antifungal treatments. Infections caused by more than one species of microbe, polymicrobial infections, are more difficult to treat and there is increasing evidence that the interactions that occur within these polymicrobial communities increase the pathogens resistance to antimicrobial therapy.

In agreement with this, a cohort of liver transplant recipients at the Queen Elizabeth Hospital Birmingham have unresolved infections despite being on long-term antibiotic and antifungal treatment. A significant percentage of these infections are polymicrobial containing both fungal and bacterial species, with Candida being the most prevalent fungal species associated with these infections. Despite treatment failure in the clinic, the pure isolates from these infections are still sensitive to antimicrobial therapy, so it is currently unclear why treatment has not been effective. These infections cause a significant level of morbidity and mortality in these patients, require very costly treatment regimens and can often result in the patient requiring a further transplant.

In this project you will investigate the mechanism(s) of altered antimicrobial susceptibility during growth within a polymicrobial community. Using isolates and samples from this cohort of liver transplant recipients you will determine whether these untreatable infections are due to heightened levels of persister cells, intracellular reservoirs of the pathogen or direct polymicrobial interactions.

Dr Hall’s group focus on the pathogenicity of Candida species and Dr Blair’s group at the University of Birmingham focus on molecular mechanisms of antimicrobial resistance.

BBSRC Strategic Research Priority: Molecules, Cells and Systems

Techniques that will be undertaken during the project:

  • Basic fungal and bacterial microbiology
  • Molecular biology (including PCR, sequencing, cloning etc)
  • Bacterial/fungal whole genome sequencing and data analysis.
  • In vitro infection assays with cells types including macrophages, hepatocytes etc.
  • Live cell imaging.

Contact: Dr Rebecca A Hall, School of Biosciences