Why do we get sick when we are stressed?

About the Project

Hypothesis: We hypothesise that host stress, via catecholamine stress hormones (norepinephrine, epinephrine, dopamine), plays a critical role in triggering the transition of Streptococcus pneumoniae from a benign coloniser in the nasopharynx to an invasive pathogen. This microbe kills millions of people every year, mainly children and elderly. This project aims to elucidate the molecular mechanisms by which S. pneumoniae senses and responds to host-derived stress signals, potentially altering its gene expression, phenotype, and virulence.

Background: Stress influences both infectious and non-infectious diseases. Catecholamines, produced during stress, are present in mucosal secretions and blood, and have been linked to increased bacterial infection severity. S. pneumoniae is a major global pathogen responsible for pneumonia, meningitis, and bacteraemia, particularly in vulnerable populations. Epidemiological and animal studies suggest that stress-related conditions and elevated catecholamine levels correlate with increased susceptibility and severity of pneumococcal disease. However, the direct impact of stress hormones on S. pneumoniae biology remains poorly understood.

Objectives:

• Determine the effects of other infection-relevant environmental factors that influence how S. pneumoniae responds to norepinephrine.
• Characterise the molecular adaptive circuit(s) that confers responsiveness to norepinephrine and its phenotypic consequences.
• Evaluate the role of pneumococcal stress hormone effector and regulatory molecules in a murine model of S. pneumoniae infection and stress.

Outputs: Understanding how S. pneumoniae responds to host stress signals will uncover novel insights into interkingdom communication and pathogen adaptation. This knowledge may inform new therapeutic strategies to mitigate infection risk in stressed individuals and improve outcomes in pneumococcal disease.

Enquiries

Project Enquiries to hy3@leicester.ac.uk

To apply please refer to

https://le.ac.uk/study/research-degrees/research-subjects/respiratory-sciences