Manchester Fungal Infection Group
Understanding and reducing the burden of human fungal diseases.
The Manchester Fungal Infection Group (MFIG) is an established international centre of excellence for fungal infection biology and translational antifungal research at The University of Manchester.
Fungal diseases kill more people annually than tuberculosis or malaria, but are very poorly understood.
Resistance to frontline antifungal agents is a growing public health concern due to extensive fungicide use in agriculture, and fungal infections are thought to contribute significantly to morbidity in influenza and COVID-19.
“Fungal diseases kill more people annually than tuberculosis or malaria…”
Manchester hosts the largest centre in the world for research into and treatment of fungal respiratory and mucosal diseases, with more than 70 university and NHS staff and students, including 10 academics/clinician academics.
Major research activites
Our research builds on a series of high-profile publications and outputs from ongoing projects funded by the MRC, BBSRC, Wellcome Trust and NIH, among others.
Using the human pathogen Aspergillus fumigatus as our main experimental system, MFIG’s research is focused on five integrated themes.
Our understanding of how fungi invade, regulate and interact with the cells, tissues and systems of the host immune system is limited.
Our research in this area is broad, and projects are investigating epithelial cell and immune cell interaction with fungi in vitro, as well as with in vivo models within murine or invertebrate hosts and human corneal models of the eye.
Considerable emphasis is being placed on live-cell imaging and the development of high throughput live-cell screens in these studies.
Genetics and genomics
All humans inhale hundreds of A. fumigatus spores each day, but only a few will develop symptoms of fungal disease.
Our understanding of the factors that affect susceptibility to aspergillosis and to other fungal diseases is limited. Our research aims to shed light on the genetic aspect of human susceptibility, in order to aid identification of at-risk groups and to help identify host pathways that may benefit from targeted supplementation.
Novel target development and drug discovery
Many of the current antifungal treatments for chronic fungal infections have multiple distressing side effects.
There are also few antifungals available to treat invasive fungal diseases, and the last antifungal target for a commercially available antifungal drug was discovered in 1974, with the antifungal being licensed in 2006.
These facts mean that the need for novel antifungals is as strong as ever. We aim to discover new antifungal drugs with novel modes of action using high throughput screening and advanced live-cell imaging techniques.
Resistance to antifungals (especially azoles) is rapidly increasing. Our research aims to investigate specific resistance mechanisms and how to combat these.
In Manchester, we have identified a series of target (cyp51A) and non-target (transporters, transcription factors, phosphoregulators and genes involved in mitochondrial function) mechanisms that control resistance to the azole class of antifungals.
We have employed this knowledge to develop a series of diagnostics to detect resistance in the clinic.
We are currently leading a multi-centre project to generate a genome-wide knockout collection in A. fumigatus to identify further mechanisms of drug resistance and pathogenicity.
Co-infections in fungal disease
Association between microorganisms is part of an evolutionary strategy to colonise and cause disease in humans.
As clinical evidence for the common occurrence of combined infection by fungi and other microorganisms increases, research into the mechanism and consequences of their interaction is becoming more relevant.
Projects in this area are focused on investigating the mechanistic by which viral or bacterial infections contribute to an impaired anti-fungal potency of the epithelium, and the impact of these interactions in the outcome of diseases.”
View selected publications below, or see a full list in the University Research Explorer.
Gago et al. CRISPR-Cas9-Mediated Gene Silencing in Cultured Human Epithelia. Methods Mol Biol. 2021;2260:37-47. doi: 10.1007/978-1-0716-1182-1_4
Rahman et al. Automated Quantitative Analysis of Airway Epithelial Cell Detachment Upon Fungal Challenge. Methods Mol Biol. 2021;2260:225-239. doi: 10.1007/978-1-0716-1182-1_16
Bertuzzi & Howell. Single-Cell Analysis of Fungal Uptake in Cultured Airway Epithelial Cells Using Differential Fluorescent Staining and Imaging Flow Cytometry. Methods Mol Biol. 2021;2260:83-109. doi: 10.1007/978-1-0716-1182-1_6
- van Rhijn et al. Development of a marker-free mutagenesis system using CRISPR-Cas9 in the pathogenic mould Aspergillus fumigatus.
Fungal Genetics and Biology, Volume 145, 2020, doi:10.1016/j.fgb.2020.103479
- Scott et al. Targeting Methionine Synthase in a Fungal Pathogen Causes a Metabolic Imbalance That Impacts Cell Energetics, Growth, and Virulence. mBio. 2020 Oct 13. doi: 10.1128/mBio.01985-20.
Bertuzzi et al. On the lineage of Aspergillus fumigatus isolates in common laboratory use. Med Mycol. 2020 Sep 17:myaa075. doi: 10.1093/mmy/myaa075.
Muñoz et al. Live-cell imaging of rapid calcium dynamics using fluorescent, genetically-encoded GCaMP probes with Aspergillus fumigatus. Fungal Genet Biol. 2020 Sep 23:103470. doi: 10.1016/j.fgb.2020.103470.
Seidel et al. Phagolysosomal Survival Enables Non-lytic Hyphal Escape and Ramification Through Lung Epithelium During Aspergillus fumigatus Infection. Front. Microbiol. 2020 11:1955. doi:10.3389/fmicb.2020.01955
- Amich et al. Three-Dimensional Light Sheet Fluorescence Microscopy of Lungs To Dissect Local Host Immune-Aspergillus fumigatus Interactions. 2020;11(1):e02752-19. Published 2020 Feb 4. doi:10.1128/mBio.02752-19
- Furukawa et al. The fungal CCAAT-binding complex and HapX display highly variable but evolutionary conserved synergetic promoter-specific DNA recognition. Nucleic Acids Research 2020
- Furukawa et al. The negative cofactor 2 complex is a key regulator of drug resistance in Aspergillus fumigatus. Nat Communications 2020
- Bowyer et al. Linking calcium signaling and mitochondrial function in fungal drug resistance. Proc Natl Acad Sci USA 2020
- Mattos et al. The Aspergillus fumigatus phosphoproteome reveals roles of high-osmolarity glycerol mitogen-activated protein kinases in promoting cell wall damage and caspofungin tolerance. MBio 2020
- Page et al. Chronic pulmonary aspergillosis commonly complicates treated pulmonary tuberculosis with residual cavitation. European Respiratory Journal 2019
- Cornely et al. Global guideline for the diagnosis and management of mucormycosis. Lancet Infect Dis 2019
- de Castro et al. Aspergillus fumigatus calcium-responsive transcription factors regulate cell wall architecture promoting stress tolerance, virulence and caspofungin resistance. Plos Genetics
- Fraczek et al. Corticosteroid treatment is associated with increased filamentous fungal burden in airways. J Allergy Clin Immunol 2018
- Gago S et al. Lung colonization by Aspergillus fumigatus is controlled by ZNF77. Nat Communications 2018
- Bertuzzi M et al. Microbial uptake by the respiratory epithelium: outcomes for host and pathogen. FEMS Microbiology Reviews 2019
Dr Riina Richardson
Clinical Senior Lecturer and Consultant for the Manchester University NHS Foundation Trust (MFT)
MFIG is part of the wider Manchester Fungal Diseases Group. This means that we work closely with the National Aspergillosis Centre and the Mycology Reference Centre. We also work collaboratively with a number of research groups around the world.
In addition, we pride ourselves on our collaborations with industrial partners.
These take many forms and include:
- research collaborations
- sponsorship of CASE studentships
- licensing partnerships
- contract research for companies.
Our partners include:
- Du Pont
- Blueberry Therapeutics
- Genon Laboratories
- PiQ Laboratories
For more information about partnerships, please contact Dr Mike Bromley by emailing firstname.lastname@example.org.
Members of MFIG are involved in several worldwide initiatives to promote education and raise awareness about fungal diseases.
Global Action Fund for Fungal Infections (GAFFI)
GAFFI aims to improve the outcomes from fungal disease globally.
Its goals are to measure the impact of serious fungal disease and support universal access to WHO-listed essential diagnostics and antifungal treatments, through education of healthcare professionals.
GAFFI’s pioneering work in Guatemala has led to an immediate fall in deaths from AIDS. Additional country programmes and the mobilisation and empowerment of GAFFI Ambassadors though advocacy training, research support and networking will see major improvements in many countries.
Leading International Fungal Education (LIFE)
The LIFE programme provides an online educational service for healthcare professionals in English and Spanish, as well as a news service for notable advances in the field. It aims to facilitate high quality diagnostics and patient care for fungal infections everywhere.
The website provides an easily read summary of the most important fungal diseases and the top pathogens, diagnostic tests and therapies, as well as an online microscopy/histology course developed in Manchester.
The Ensembl Fungi resource
MFIG has contributed genomic data for eight different Aspergillus species and two strains for A. fumigatus to Ensembl Fungi (fungi.ensembl.org). This data has been collated as a central resource to support the Aspergillus research community.
This work arose from the initial sequencing projects for Aspergillus fumigatus, of which members of MFIG were heavily involved.
- Ensembl Fungi
- Machida, M., Asai, K., Sano, M. et al. Genome sequencing and analysis of Aspergillus oryzae. Nature 438, 1157–1161 (2005)
The Aspergillus Website
It provides an encyclopaedia of Aspergillus for doctors, scientists, patients and their relatives.
COFUN - Genome-wide knock out project
COFUN is a Wellcome Trust-funded project that aims to generate knockout mutants for all of the coding genes in the human pathogen Aspergillus fumigatus. In total, around 10,000 strains will be generated.
For more information about our international links and impact, please contact Prof David Denning by emailing email@example.com.
Training future scientists and clinician
It is important for us to inspire, promote and support the next generation of researchers in medical mycology. We are committed to this at all levels of study, and our PIs, staff and postdoctoral researchers teach on numerous courses.
Related master’s courses
We provide training and support for MSc, MRes and MSci students from various master’s courses doing research projects. These include:
- Bioinformatics and Systems Biology (MSc)
- Biology (MSci)
- Biomedical Sciences (MSci)
- Clinical Bioinformatics (PGCert)
- Clinical Immunology (MSc)
- Genomic Medicine (MSc)
- Infection Biology (MRes)
- Medical Microbiology (MSc)
- Microbiology (MSci)
- Molecular Pathology (MSc)
Doctoral training and postgraduate research
Within the group, we currently have around 12 PhD students and 5 postdoctoral researchers, drawn from all over the world.
We enable students to undertake a research project that will further improve their understanding of medical mycology. We also provide a framework of postgraduate research training in research council-funded doctoral training partnerships.
- Medical Research Council Doctoral Training Partnership
- BBSRC Doctoral Training Partnership (including CASE studentships)
For more information about teaching and learning within the group, please contact Dr Margherita Bertuzzi.