Summary
We’re hoping to help overcome the challenge of culturing Pneumocystis, a deadly human pathogen, by using innovative in silico metabolic modelling and experimental approaches. The outcomes could be game-changing for the Medical Mycology community, enabling a deeper understanding of Pneumocystis immunology and pathobiology. This could help with early detection of Pneumocystis infections, susceptibility testing, analysis of the antimicrobial drug resistance that is emerging in Pneumocystis, and the development of new treatments for Pneumocystis infections.
What are we doing?
There is a major bottleneck in Pneumocystis research caused by the challenge in growing Pneumocystis independently of its host. We hope to overcome this by using an innovative approach that combines in silico metabolic modelling, machine learning, and experimental phenotyping to define in vitro and/or ex vivo growing conditions. This will help us to gain insights into its pathobiology and drug sensitivities, and so improve treatment strategies and health outcomes for affected people.
How are we doing it?
We’re collaborating with experts in Metabolic Modeling, Bioinformatics, Flux Balance Analysis, and Machine Learning. Using new genomic information, we’ve developed a mathematical model of Pneumocystis growth and metabolism, revealing more about what it needs to thrive. To test these predictions, our collaborators set up experiments to find the best conditions for Pneumocystis to grow in the lab. Our initial results show that certain conditions can help the fungus survive longer.
What happens next?
Our next step is to turn prolonged survival into sustained growth. We will study Pneumocystis growth outside its host by using cell cultures and lung tissue samples. We’ll translate the metabolic model we developed using a model Pneumocystis species (P. murina) to provide invaluable insights into the pathobiology and drug sensitivities of the human pathogen, Pneumocystis jirovecii. It will be important to understand how Pneumocystis jirovecii behaves and how it responds to different drugs.
Collaborators
Prof Alistair Brown (University of Exeter, MRC Centre for Medical Mycology)
Dr Jennifer C. Hoving (University of Cape Town, Institute of Infectious Disease and Molecular Medicine, AFRICA MRC CMM Medical Mycology Unit)
Dr Rachael Dangarembizi (University of Cape Town, Institute of Infectious Disease and Molecular Medicine, AFRICA MRC CMM Medical Mycology Unit)
Dr Lucian Duvenage (University of Cape Town, Institute of Infectious Disease and Molecular Medicine, AFRICA MRC CMM Medical Mycology Unit)
Dr Elena Zamaraeva (Leverhulme Research Centre for Functional Materials Design, Materials Innovation Factory, University of Liverpool, Liverpool, United Kingdom)
Gencovery, Lyon, France
Prof Ivana Gudelj (University of Exeter, Living Systems Institute)
People involved
Prof Gordon Brown
Clinical Mycology Theme Lead
Prof Adilia Warris
Clinical Mycology Theme Lead, Director of Training (ACD Lead)