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The impact of air pollution on bacterial infection and host immune responses

Primary Supervisor: Professor Julie Morrissey, Department of Genetics and Genome Biology

Secondary supervisor: Professor Julian Ketley, Professor Paul Monks

PhD project title: The impact of air pollution on bacterial infection and host immune responses.

University of Registration: University of Leicester

Project outline:

Air pollution is the world’s largest single environmental health risk, being responsible for an eighth of all global deaths per year (World Health Organisation, 2017). Particulate matter (PM), a key component of air pollution, is strongly associated with exacerbation of chronic respiratory disease such as COPD and asthma, and adverse effects with chronic skin diseases. There is also an association with increased infectious disease, including community acquired pneumonia, infective endocarditis, infection of cystic fibrosis patients, otitis media and chronic rhinosinusitis. However, until very recently, how PM directly affects respiratory bacteria has received no attention, which is surprising considering the importance of these bacteria in maintaining health and as pathogens.  

Our studies showed that exposure to PM alters Streptococcus pneumoniae and Staphylococcus aureus respiratory tract colonisation and induces changes in biofilm formation and importantly altered the tolerance of biofilms to antibiotics (Hussey et al., 201).

Our recent data show that PM also alters the interaction of S. aureus, and Haemophilus influenzae and Moraxella catarrhalis, key pathogens in the exacerbation of COPD, adhesion and invasion of human epithelial cells, impacts epithelial cell integrity and modifies the immune response. Our transcriptional data show that PM directly alters bacterial global gene expression significantly increasing the risk of host colonisation and evasion of the immune system.

Therefore, the aim of this project is to further explore this novel mechanism of air pollution and determine how PM affects bacterial infection. This project will increase our understanding of how air pollution causes increased infectious disease and exacerbates chronic respiratory disease.

Objectives are:

  1. Establish the molecular mechanisms involved in the PM-responsive regulation of virulence factors.
  2. Determine the importance of PM-regulated biological pathways in

(a) infection and antimicrobial resistance

(b) survival against human innate immunity.

Research plan.

This project will focus on respiratory bacteria associated with community acquired pneumonia or skin infection, or changes in COPD severity. The interplay between bacteria, host and air pollution will be investigated using molecular microbiology, transcriptional analysis, tissue cell culture, flow cytometry and advanced imaging microscopy techniques. This is an exciting, inter-disciplinary project with healthcare implications. The student will benefit from clinical data on the impact of air pollution on microbial communities, clinical samples and project related investigations with respiratory and infectious disease clinicians.

Reference:

  1. Ramsheh et al. 2021. The Lancet Microbe 2(7) e300-e310. Hussey et al. 2017. Environmental Microbiology 19(5) 1868-1880.

BBSRC Strategic Research Priority: Understanding the Rules of Life: Microbiology

    Techniques that will be undertaken during the project:

    This multi-disciplinary project involving microbiologists, and atmospheric chemists will include a wide range of molecular microbiology including transcriptional analysis using next generation sequencing, and a range of ex vivo infection models and cutting-edge imaging and chemical analysis.

    Contact: Professor Julie Morrissey, University of Leicester