Summary
Establishing a human plasma-based in vitro system to co-culture Cryptococcus and Mycobacterium to simulate a scenario where these two microbes are present within the same patient.
What are we doing?
Infections caused by Cryptococcus neoformans (C. neoformans) and Mycobacterium tuberculosis (Mtb) result in high mortality. Clinical cases of co-infections of these are rising, but the full epidemiological scope is unknown. Despite this, evidence shows that in areas where both are endemic, coinciding with HIV infection, the prevalence of co-infection increases significantly. Notably Cryptococcus-Mtb co-infection significantly increases the risk of death relative to Cryptococcus infection alone. Worryingly, when Mtb is left untreated, C. neoformans becomes resistant to antifungal medication.
We aim to determine whether Mtb or BCG (Mtb vaccine strain) influence the growth and severity of C. neoformans and characterise which human plasma metabolites are altered during co-infection.
How are we doing it?
In this project, we are establishing a method using non-radioactive isotope tracers for hydrogen-2, Carbon-13, and Nitrogen-15 to accurately measure growth rates and metabolic needs of the various C. neoformans cell populations in host-mimicking conditions. We will carry out metabolomics and use transcriptomics to map gene networks that are altered when C. neoformans is co-cultured with Mtb or BCG.
What happens next?
This work will lay foundation for the creation of a predictive plasma biomarker signature for HIV positive individuals at risk of Cryptococcus-Mtb pathogenesis.
People Involved
Dr Liliane Mukaremera, University of Exeter