Exploring the Respiratory mycobiome in Tuberculosis

About the Project

The latest WHO reports that around 10.7 million people were diagnosed and 1.23 million people died from the curable and preventable disease tuberculosis (TB) in 2024, putting it in the top 10 causes of death worldwide1. TB is caused by infection with the bacterial pathogen Mycobacterium tuberculosis. M. tuberculosis infection is influenced by a number of factors including nutrition, immune dysregulation, and the genetics of both the host and the pathogen. However, these factors are unable to fully explain the variability of pathogenesis observed in TB infections.

Improvements in sequencing technologies over the last decade has allowed in-depth exploration of the microbial community associated with the human body, known as the human microbiome. Studies using these technologies have provided strong evidence for associations between the microbiome and the bodies responses to infection. Studies in both human subjects and mouse models have revealed altered bacterial profiles associated active TB and treatment, however as yet no studies have explored the mycobiome in these patients.

Fungal respiratory diseases, particularly in those with underlying illness, are increasingly problematic. These infections are associated with poor clinical outcomes, exacerbation of symptoms and increased mortality. A recent systematic review, suggested that around 9% of TB patients are co-infected with Aspergillus during treatment, this increased to 13% after treatment completion2. These number may be skewed by the low sensitivity of fungal culture, estimated to miss around 50% of infections.

This project aims to explore the diversity and composition of the respiratory mycobiome in patients with pulmonary tuberculosis infection and explore how the fungal community influences M. tuberculosis phenotypes. We hypothesise that fungal communities within the lung play a role in the development and virulence of TB infection and may influence disease progression.

Using a combination of culture and high throughput sequencing the influence of fungal communities on the growth and virulence of M. tuberculosis infection will be explored. This work is a vital step forward in our understanding of the pulmonary TB and the drivers of disease outcomes.

This exciting project is hosted by the University of Leicester and benefit from close links to the Leicester NIHR Biomedical Research Centre. You will gain extensive knowledge of some of the most important chronic respiratory conditions in humans and employ state-of-the-art techniques to study fungal airway disease