The genetic basis of niche-specific virulence in Streptococcus pneumoniae
The pneumococcus is a bacterium that causes severe diseases throughout the world, but particularly in poorer countries. It is the most common cause of death from infectious disease in children under five. We don't have a vaccine that protects against every type of pneumococcus, and what makes pneumococcus so deadly is the ability to adapt to different challenges in different sites in the human body. Many people have pneumococcus living harmlessly in their noses and mouths, but it is also able to survive in the lungs (where it can cause pneumonia) and the lining of the brain (where it causes meningitis).
This five-year Wellcome Trust and Royal Society-funded project aims to explain how pneumococcus thrives in different places. By comparing the genes of bacteria that cause different types of disease, we will be able to find out which genes are required to infect certain organs. We will then construct bacteria that lack these genes and find out if they are still able to cause disease. This will help us understand changes in the ‘safe’ bacteria in our noses which allows them to cause disease. We aim to find important bacterial proteins that could be targeted in new vaccines or drugs that could control pneumococcal disease.
Immune modulation in pneumococcal carriage and invasive disease
In collaboration with Aras Kadioglu in IGH I have been working on the role of immune modulatory pathways in resistance to invasive pneumococcal disease. In particular, I have been interested in the role of T regulatory cells in the nasopharynx and lung and their roles in organising the inflammatory response in order to prevent bacterial dissemination within the host. We have also been investigating the factors that drive the progression of carriage to symptomatic disease. These including co-infecting pathogens, particulate pollution and extremes of temperature.
Drivers of Pseudomonas aeruginosa adaptation in the respiratory tract.
Pseudomonas aeruginosa causes debilitating and life-threatening lung infections in people with cystic fibrosis. These chronic infections are often highly resistant to antimicrobial treatment. In collaboration with Aras Kadioglu, Jo Fothergill and Craig Winstanley in IGH I have been investigating the early genetic changes that occur in Pseudomonas aeruginosa in the upper respiratory tract. We believe the upper airways provide a protected niche in which bacterial adaptation can occur prior to seeding into the lungs and establishment of chronic (and treatment-resistant) infection and we have developed a novel infection system that models this process. We are using this model to study early bacterial adaptation and as a clinically relevant system in which to test novel therapeutics.
Research Group Membership
Inhalable Aerosol Light Source for Controlling Drug-Resistant Bacterial Lung Infections - Light4Lungs
December 2019 - November 2023
Disrupting bacterial signaling pathways to break antibiotic resistance
BRITISH SOCIETY FOR ANTIMICROBIAL CHEMOTHERAPY (UK)
October 2018 - September 2019
Epidemiology, Prevention, and Treatment of Influenza and Other Respiratory Infections in a Malaria-Endemic Area of Malawi with High HIV Prevalence. (Year 3)
CENTERS FOR DISEASE CONTROL AND PREVENTION (CDC) (USA)
August 2016 - July 2020
Identification of niche-specific virulence factors via experimental evolution of Streptococcus pneumoniae
WELLCOME TRUST (UK)
October 2017 - October 2022
The role of resistance to host-derived antimicrobials in establishment of chronic Pseudomonas aeruginosa infection in children with cystic fibrosis.
BRITISH LUNG FOUNDATION (UK)
September 2016 - February 2018
The role of immune tolerance and regulation in pneumococcal carriage and invasive disease
MEDICAL RESEARCH COUNCIL (MRC)
June 2017 - May 2022
Discovery of Pseudomonas aeruginosa mutations associated with chronic lung infection in children with CF.
ACTION MEDICAL RESEARCH (UK)
August 2017 - March 2021
A novel model of Streptococcus pneumoniae interactions with host cell in the upper airways.
THE BRITISH INFECTION ASSOCIATION (UK)
January 2015 - December 2016
How do interactions between S. pneumoniae and NT H. influenzae influence upper respiratory tract carriage density and duration?
GLAXOSMITHKLINE BIOLOGICALS S.A. (BELGIUM)
April 2014 - August 2016
Bridging and accelerating the translation of novel scientific findings for health and wealth gain
MEDICAL RESEARCH COUNCIL (MRC)
March 2014 - August 2015