Imperial College London

Professor Matthew Fisher

Faculty of MedicineSchool of Public Health

Professor of Fungal Disease Epidemiology
 
 
 
//

Contact

 

matthew.fisher Website

 
 
//

Location

 

1113Building E - Sir Michael UrenWhite City Campus

//

Summary

 

Publications

Publication Type
Year
to

228 results found

Furukawa T, van Rhijn N, Chown H, Rhodes J, Alfuraiji N, Fortune-Grant R, Bignell E, Fisher MC, Bromley Met al., 2022, Exploring a novel genomic safe-haven site in the human pathogenic mould br Aspergillus fumigatus, FUNGAL GENETICS AND BIOLOGY, Vol: 161, ISSN: 1087-1845

Journal article

Rhodes J, 2022, Population genomics confirms acquisition of drug resistant Aspergillus fumigatus infection by humans from the environment, Nature Microbiology, Vol: 7, ISSN: 2058-5276

Infections caused by the fungal pathogen Aspergillus fumigatus are increasingly resistant to first-line azole antifungal drugs. However, despite its clinical importance, little is known about how susceptible patients acquire infection from drug resistant genotypes in the environment. Here, we present a population genomic analysis of 218 A. fumigatus from across the United Kingdom and Ireland (comprising 153 clinical isolates from 143 patients, and 65 environmental isolates). First, phylogenomic analysis shows strong genetic structuring into two clades (‘A’ and ‘B’) with little interclade recombination and the majority of environmental azole resistance found within Clade A. Secondly, we show occurrences where azole resistant isolates of near identical genotypes were obtained from both environmental and clinical sources, indicating with high confidence the infection of patients with resistant isolates transmitted from the environment. Third, genome-scans identified selective sweeps across multiple regions indicating a polygenic basis to the trait in some genetic backgrounds. These signatures of positive selection are seen for loci containing the canonical genes encoding fungicide resistance in the ergosterol biosynthetic pathway, whilst other regions under selection have no defined function. Lastly, pangenome analysis identified genes linked to azole resistance and novel resistance mechanisms. Understanding the environmental drivers and genetic basis of evolving fungal drug resistance needs urgent attention, especially in light of increasing numbers of patients with severe viral respiratory tract infections who are susceptible to opportunistic fungal superinfections.

Journal article

Fisher MC, Alastruey-Izquierdo A, Berman J, Bicanic T, Bignell EM, Bowyer P, Bromley M, Brueggemann R, Garber G, Cornely OA, Gurr SJ, Harrison TS, Kuijper E, Rhodes J, Sheppard DC, Warris A, White PL, Xu J, Zwaan B, Verweij PEet al., 2022, Tackling the emerging threat of antifungal resistance to human health, NATURE REVIEWS MICROBIOLOGY, ISSN: 1740-1526

Journal article

Furukawa T, van Rhijn N, Chown H, Rhodes J, Alfuraji N, Fortune-Grant R, Bignell E, Fisher MC, Bromley Met al., 2022, Exploring a novel genomic safe-haven site in the human pathogenic mould <i>Aspergillus fumigatus</i>

<jats:title>ABSTRACT</jats:title><jats:p><jats:italic>Aspergillus fumigatus</jats:italic> is the most important airborne fungal pathogen and allergen of humans causing high morbidity and mortality worldwide. The factors that govern pathogenicity of this organism are multi-factorial and are poorly understood. Molecular tools to dissect the mechanisms of pathogenicity in <jats:italic>A. fumigatus</jats:italic> have improved significantly over the last 20 years however many procedures have not been standardised for <jats:italic>A. fumigatus</jats:italic>. Here, we present a new genomic safe-haven locus at the site of an inactivated transposon, named SH-<jats:italic>aft4</jats:italic>, which can be used to insert DNA sequences in the genome of this fungus without impacting its phenotype. We show that we are able to effectively express a transgene construct from the SH-<jats:italic>aft4</jats:italic> and that natural regulation of promoter function is conserved at this site. Furthermore, the SH-<jats:italic>aft4</jats:italic> locus is highly conserved in the genome of a wide range of clinical and environmental isolates including the isolates commonly used by many laboratories CEA10, Af293 and ATCC46645, allowing a wide range of isolates to be manipulated. Our results show that the <jats:italic>aft4</jats:italic> locus can serve as a site for integration of a wide range of genetic constructs to aid functional genomics studies of this important human fungal pathogen.</jats:p>

Journal article

Bates KA, Sommer U, Hopkins KP, Shelton JMG, Wierzbicki C, Sergeant C, Tapley B, Michaels CJ, Schmeller DS, Loyau A, Bosch J, Viant MR, Harrison XA, Garner TWJ, Fisher MCet al., 2022, Microbiome function predicts amphibian chytridiomycosis disease dynamics, Microbiome, Vol: 10, ISSN: 2049-2618

Background The fungal pathogen Batrachochytrium dendrobatidis (Bd) threatens amphibian biodiversity and ecosystem stability worldwide. Amphibian skin microbial community structure has been linked to clinical outcome of Bd infections, yet its overall functional importance is poorly understood. Methods Microbiome taxonomic and functional profiles were assessed using high-throughput bacterial 16S rRNA and fungal ITS2 gene sequencing, bacterial shotgun metagenomics and skin mucosal metabolomics. We sampled 56 wild midwife toads (Alytes obstetricans) from montane populations exhibiting Bd epizootic or enzootic disease dynamics. In addition, to assess whether disease-specific microbiome profiles were linked to microbe-mediated protection or Bd-induced perturbation, we performed a laboratory Bd challenge experiment whereby 40 young adult A. obstetricans were exposed to Bd or a control sham infection. We measured temporal changes in the microbiome as well as functional profiles of Bd exposed and control animals at peak infection. Results Microbiome community structure and function differed in wild populations based on infection history and in experimental control versus Bd-exposed animals. Bd exposure in the laboratory resulted in dynamic changes in microbiome community structure and functional differences, with infection clearance in all but one infected animal. Sphingobacterium, Stenotrophomonas and an unclassified Commamonadaceae were associated with wild epizootic dynamics and also had reduced abundance in laboratory Bd-exposed animals that cleared infection, indicating a negative association with Bd resistance. This was further supported by microbe-metabolite integration which identified functionally relevant taxa driving disease outcome, of which Sphingobacterium and Bd were most influential in wild epizootic dynamics. The strong correlation between microbial taxonomic community composition and skin metabolome in the laboratory and field are inconsistent with microbia

Journal article

Shelton J, Collins R, Uzzell CB, Alghamdi A, Dyer PS, Singer AC, Fisher Met al., 2022, Citizen-science surveillance of triazole-resistant Aspergillus fumigatus in UK residential garden soils, Applied and Environmental Microbiology, Vol: 88, Pages: 1-12, ISSN: 0099-2240

Compost is an ecological niche for Aspergillus fumigatus due to its role as a decomposer of organic matter and its ability to survive the high temperatures associated with the composting process. Subsequently, composting facilities are associated with high levels of A. fumigatus spores that are aerosolized from compost and cause respiratory illness in workers. In the UK, gardening is an activity enjoyed by individuals of all ages, and it is likely that they are being exposed to A. fumigatus spores when handling commercial compost or compost they have produced themselves. In the present study, 246 citizen scientists collected 509 soil samples from locations in their gardens in the UK, from which were cultured 5,174 A. fumigatus isolates. Of these isolates, 736 (14%) were resistant to tebuconazole: the third most-sprayed triazole fungicide in the UK, which confers cross-resistance to the medical triazoles used to treat A. fumigatus lung infections in humans. These isolates were found to contain the common resistance mechanisms in the A. fumigatus cyp51A gene TR34/L98H or TR46/Y121F/T289A, as well as the less common resistance mechanisms TR34, TR53, TR46/Y121F/T289A/S363P/I364V/G448S, and (TR46)2/Y121F/M172I/T289A/G448S. Regression analyses found that soil samples containing compost were significantly more likely to grow tebuconazole-susceptible and tebuconazole-resistant A. fumigatus strains than those that did not and that compost samples grew significantly higher numbers of A. fumigatus than other samples.IMPORTANCE The findings presented here highlight compost as a potential health hazard to individuals with predisposing factors to A. fumigatus lung infections and as a potential health hazard to immunocompetent individuals who could be exposed to sufficiently high numbers of spores to develop infection. Furthermore, we found that 14% of A. fumigatus isolates in garden soils were resistant to an agricultural triazole, which confers cross-resistance to medical triazo

Journal article

Duong T-MN, Le T-V, Tran K-LH, Nguyen P-T, Nguyen B-PT, Nguyen T-A, Nguyen H-LP, Nguyen B-NT, Fisher MC, Rhodes J, Marks G, Fox GJ, Chen SC-A, Walsh MG, Barrs VR, Talbot J, Halliday CL, Sorrell TC, Day JN, Beardsley Jet al., 2021, Azole-resistant Aspergillus fumigatus is highly prevalent in the environment of Vietnam, with marked variability by land use type, Environmental Microbiology, Vol: 23, Pages: 7632-7642, ISSN: 1462-2912

Azole-resistant environmental Aspergillus fumigatus presents a threat to public health but the extent of this threat in Southeast Asia is poorly described. We conducted environmental surveillance in the Mekong Delta region of Vietnam, collecting air and ground samples across key land-use types, and determined antifungal susceptibilities of Aspergillus section Fumigati (ASF) isolates and azole concentrations in soils. Of 119 ASF isolates, 55% were resistant (or non-wild type) to itraconazole, 65% to posaconazole and 50% to voriconazole. Azole resistance was more frequent in A. fumigatus sensu stricto isolates (95%) than other ASF species (32%). Resistant isolates and agricultural azole residues were overrepresented in samples from cultivated land. cyp51A gene sequence analysis showed 38/56 resistant A. fumigatus sensu stricto isolates carried known resistance mutations, with TR34/L98H most frequent (34/38).

Journal article

Bosch J, Thumsová B, López-Rojo N, Pérez J, Alonso A, Fisher MC, Boyero Let al., 2021, Microplastics increase susceptibility of amphibian larvae to the chytrid fungus Batrachochytrium dendrobatidis., Scientific Reports, Vol: 11, Pages: 1-7, ISSN: 2045-2322

Microplastics (MPs), a new class of pollutants that pose a threat to aquatic biodiversity, are of increasing global concern. In tandem, the amphibian chytrid fungus Batrachochytrium dendrobatidis (Bd) causing the disease chytridiomycosis is emerging worldwide as a major stressor to amphibians. We here assess whether synergies exist between this infectious disease and MP pollution by mimicking natural contact of a highly susceptible species (midwife toads, Alytes obstetricans) with a Bd-infected reservoir species (fire salamanders, Salamandra salamandra) in the presence and absence of MPs. We found that MP ingestion increases the burden of infection by Bd in a dose-dependent manner. However, MPs accumulated to a greater extent in amphibians that were not exposed to Bd, likely due to Bd-damaged tadpole mouthparts interfering with MP ingestion. Our experimental approach showed compelling interactions between two emergent processes, chytridiomycosis and MP pollution, necessitating further research into potential synergies between these biotic and abiotic threats to amphibians.

Journal article

Wacker T, Helmstetter N, Wilson D, Fisher MC, Studholme DJ, Farrer RAet al., 2021, Two-speed genome expansion drives the evolution of pathogenicity in animal fungal pathogens

<jats:title>Abstract</jats:title><jats:p>The origins of virulence in amphibian-infecting chytrids <jats:italic>Batrachochytrium dendrobatidis</jats:italic> (<jats:italic>Bd</jats:italic>) and <jats:italic>Batrachochytrium salamandrivorans</jats:italic> (<jats:italic>Bsal)</jats:italic> are largely unknown. Here, we use deep nanopore sequencing of <jats:italic>Bsal</jats:italic> and comparative genomics against 21 high-quality genome assemblies that span the fungal Chytridiomycota. <jats:italic>Bsal</jats:italic> has the most repeat-rich genome, comprising 40.9% repetitive elements, which has expanded to more than 3X the length of its conspecific <jats:italic>Bd</jats:italic>. M36 metalloprotease virulence factors are highly expanded in <jats:italic>Bsal</jats:italic> and 53% of the 177 unique genes are flanked by transposable elements, suggesting repeat-driven expansion. The largest M36 sub-family are mostly (84%) flanked upstream by a novel LINE element, a repeat superfamily implicated with gene copy number variations. We find that <jats:italic>Bsal</jats:italic> has a highly compartmentalized genome architecture, with virulence factors enriched in gene-sparse/repeat-rich compartments, while core conserved genes occur in gene-rich/repeat-poor compartments. This is a hallmark of two-speed genome evolution. Furthermore, genes with signatures of positive selection in <jats:italic>Bd</jats:italic> are enriched in repeat-rich regions, suggesting they are a cradle for chytrid pathogenicity evolution, and <jats:italic>Bd</jats:italic> also has a two-speed genome. This is the first evidence of two-speed genomes in any animal pathogen, and sheds new light on the evolution of fungal pathogens of vertebrates driving global declines and extinctions.</jats:p>

Journal article

Rocchi S, Sewell TR, Valot B, Godeau C, Laboissiere A, Millon L, Fisher MCet al., 2021, Molecular epidemiology of azole-resistant Aspergillus fumigatus in France shows patient and healthcare links to environmentally occurring genotypes, Frontiers in Cellular and Infection Microbiology, Vol: 11, Pages: 1-11, ISSN: 2235-2988

Resistance of the human pathogenic fungus Aspergillus fumigatus to antifungal agents is on the rise. However, links between patient infections, their potential acquisition from local environmental sources, and links to global diversity remain cryptic. Here, we used genotyping analyses using nine microsatellites in A. fumigatus, in order to study patterns of diversity in France. In this study, we genotyped 225 local A. fumigatus isolates, 112 azole susceptible and 113 azole resistant, collected from the Bourgogne-Franche-Comté region (Eastern France) and sampled from both clinical (n = 34) and environmental (n = 191) sources. Azole-resistant clinical isolates (n = 29) were recovered mainly from cystic fibrosis patients and environmental isolates (n = 84) from market gardens and sawmills. In common with previous studies, the TR34/L98H allele predominated and comprised 80% of resistant isolates. The genotypes obtained for these local TR34/L98H isolates were integrated into a broader analysis including all genotypes for which data are available worldwide. We found that dominant local TR34/L98H genotypes were isolated in different sample types at different dates (different patients and types of environments) with hospital air and patient’s isolates linked. Therefore, we are not able to rule out the possibility of some nosocomial transmission. We also found genotypes in these same environments to be highly diverse, emphasizing the highly mixed nature of A. fumigatus populations. Identical clonal genotypes were found to occur both in the French Eastern region and in the rest of the world (notably Australia), while others have not yet been observed and could be specific to our region. Our study demonstrates the need to integrate patient, healthcare, and environmental sampling with global databases in order to contextualize the local-scale epidemiology of antifungal resistant aspergillosis.

Journal article

Alvarado-Rybak M, Acuña P, Peñafiel-Ricaurte A, Sewell TR, O'Hanlon SJ, Fisher MC, Valenzuela-Sánchez A, Cunningham AA, Azat Cet al., 2021, Chytridiomycosis outbreak in a Chilean giant frog (Calyptocephalella gayi) captive breeding program: genomic characterization and pathological findings, Frontiers in Veterinary Science, Vol: 8, ISSN: 2297-1769

Emerging infectious diseases in wildlife are increasingly associated with animal mortality and species declines, but their source and genetic characterization often remains elusive. Amphibian chytridiomycosis, caused by the fungus Batrachochytrium dendrobatidis (Bd), has been associated with catastrophic and well-documented amphibian population declines and extinctions at the global scale. We used histology and whole-genome sequencing to describe the lesions caused by, and the genetic variability of, two Bd isolates obtained from a mass mortality event in a captive population of the threatened Chilean giant frog (Calyptocephalella gayi). This was the first time an association between Bd and high mortality had been detected in this charismatic and declining frog species. Pathological examinations revealed that 30 dead metamorphosed frogs presented agnathia or brachygnathia, a condition that is reported for the first time in association with chytridiomycosis. Phylogenomic analyses revealed that Bd isolates (PA1 and PA2) from captive C. gayi group with other Bd isolates (AVS2, AVS4, and AVS7) forming a single highly supported Chilean Bd clade within the global panzootic lineage of Bd (BdGPL). These findings are important to inform the strengthening of biosecurity measures to prevent the impacts of chytridiomycosis in captive breeding programs elsewhere.

Journal article

Sewell TR, Longcore J, Fisher MC, 2021, Batrachochytrium dendrobatidis, TRENDS IN PARASITOLOGY, Vol: 37, Pages: 933-934, ISSN: 1471-4922

Journal article

Brackin A, Hemmings S, Fisher M, Rhodes Jet al., 2021, Fungal genomics in respiratory medicine: what, how and when?, Mycopathologia, Vol: 186, Pages: 589-608, ISSN: 0301-486X

Respiratory infections caused by fungal pathogens present a growing global healthconcern and are a major cause of death in immunocompromised patients. Worryingly,coronavirus disease-19 (COVID-19) resulting in acute respiratory distress syndrome,has been shown to predispose some patients to fungal co-infection and secondarypulmonary aspergillosis. Aspergillosis is most commonly caused by the fungalpathogen Aspergillus fumigatus and primarily treated using the triazole drug group,however in recent years, this fungus has been rapidly gaining resistance against theseantifungals. This is of serious clinical concern as multi-azole resistant forms ofaspergillosis have a higher risk of mortality when compared against azole-susceptibleinfections. With the increasing numbers of COVID-19 and other classes ofimmunocompromised patients, early diagnosis of fungal infections is critical to ensuringpatient survival. However, time-limited diagnosis is difficult to achieve with currentculture-based methods. Advances within fungal genomics have enabled moleculardiagnostic methods to become a fast, reproducible, and cost-effective alternative fordiagnosis of respiratory fungal pathogens and detection of antifungal resistance. Herewe describe what techniques are currently available within molecular diagnostics, howthey work and when they have been used.

Journal article

Di Paolo M, Hewitt L, Nwankwo E, Ni M, Vidal-Diaz A, Fisher MC, Armstrong-James D, Shah Aet al., 2021, A retrospective 'real-world' cohort study of azole therapeutic drug monitoring and evolution of antifungal resistance in cystic fibrosis (vol 12, dlab086, 2021), JAC-ANTIMICROBIAL RESISTANCE, Vol: 3

Journal article

de Carvalho JA, Beale MA, Hagen F, Fisher MC, Kano R, Bonifaz A, Toriello C, Negroni R, Rego RSDM, Gremiao IDF, Pereira SA, de Camargo ZP, Rodrigues AMet al., 2021, Trends in the molecular epidemiology and population genetics of emerging Sporothrix species, STUDIES IN MYCOLOGY, ISSN: 0166-0616

Journal article

Roberto TN, de Carvalho JA, Beale MA, Hagen F, Fisher MC, Hahn RC, de Camargo ZP, Rodrigues AMet al., 2021, Exploring genetic diversity, population structure, and phylogeography in Paracoccidioides species using AFLP markers., Studies in Mycology, Vol: 100, Pages: 100131-100131, ISSN: 0166-0616

Paracoccidioidomycosis (PCM) is a life-threatening systemic fungal infection acquired after inhalation of Paracoccidioides propagules from the environment. The main agents include members of the P. brasiliensis complex (phylogenetically-defined species S1, PS2, PS3, and PS4) and P. lutzii. DNA-sequencing of protein-coding loci (e.g., GP43, ARF, and TUB1) is the reference method for recognizing Paracoccidioides species due to a lack of robust phenotypic markers. Thus, developing new molecular markers that are informative and cost-effective is key to providing quality information to explore genetic diversity within Paracoccidioides. We report using new amplified fragment length polymorphism (AFLP) markers and mating-type analysis for genotyping Paracoccidioides species. The bioinformatic analysis generated 144 in silico AFLP profiles, highlighting two discriminatory primer pairs combinations (#1 EcoRI-AC/MseI-CT and #2 EcoRI-AT/MseI-CT). The combinations #1 and #2 were used in vitro to genotype 165 Paracoccidioides isolates recovered from across a vast area of South America. Considering the overall scored AFLP markers in vitro (67-87 fragments), the values of polymorphism information content (PIC = 0.3345-0.3456), marker index (MI = 0.0018), effective multiplex ratio (E = 44.6788-60.3818), resolving power (Rp = 22.3152-34.3152), discriminating power (D = 0.5183-0.5553), expected heterozygosity (H = 0.4247-0.4443), and mean heterozygosity (H avp  = 0.00002-0.00004), demonstrated the utility of AFLP markers to speciate Paracoccidioides and to dissect both deep and fine-scale genetic structures. Analysis of molecular variance (AMOVA) revealed that the total genetic variance (65-66 %) was due to variability among P. brasiliensis complex and P. lutzii (PhiPT = 0.651-0.658, P < 0.0001), supporting a highly structured population. Heterothallism was

Journal article

Di Paolo M, Hewitt L, Nwankwo E, Ni M, Vidal-Diaz A, Fisher MC, Armstrong-James D, Shah Aet al., 2021, Erratum to: A retrospective 'real-world' cohort study of azole therapeutic drug monitoring and evolution of antifungal resistance in cystic fibrosis., JAC Antimicrob Resist, Vol: 3

[This corrects the article DOI: 10.1093/jacamr/dlab026.].

Journal article

Shelton J, Collins R, Uzzell C, Alghamdi A, Dyer P, Singer A, Fisher Met al., 2021, Citizen-science surveillance of triazole-resistant Aspergillus fumigatus in UK residential garden soils, Publisher: Cold Spring Harbor Laboratory

Compost is an ecological niche for Aspergillus fumigatus due to its role as a decomposer of organic matter and its ability to survive the high temperatures associated with the composting process. Subsequently, composting facilities are associated with high levels of A. fumigatus spores that are aerosolised from compost and cause respiratory illness in workers. In the UK, gardening is an activity enjoyed by individuals of all ages and it is likely that they are being exposed to A. fumigatus spores when handling commercial compost or compost they have produced themselves. In this study, 246 citizen scientists collected 509 soil samples from locations in their garden in the UK, from which were cultured 5,174 A. fumigatus isolates. Of these isolates, 736 (14%) were resistant to tebuconazole: the third most-sprayed triazole fungicide in the UK, which confers cross-resistance to the medical triazoles used to treat A. fumigatus lung infections in humans. These isolates were found to contain the common resistance mechanisms in the A. fumigatus cyp51A gene TR 34 /L98H or TR 46 /Y121F/T289A, and less common resistance mechanisms TR 34 , TR 53 , TR 46 /Y121F/T289A/S363P/I364V/G448S and (TR 46 ) 2 /Y121F/M172I/T289A/G448S. Regression analyses found that soil samples containing compost were significantly more likely to grow susceptible and tebuconazole-resistant A. fumigatus than those that did not, and that compost samples grew significantly higher numbers of A. fumigatus than other samples. <h4>Importance</h4> These findings highlight compost as a potential health hazard to individuals with pre-disposing factors to A. fumigatus lung infections, and a potential health hazard to immunocompetent individuals who could be exposed to sufficiently high numbers of spores to develop infection. This raises the question of whether compost bags should carry additional health warnings regarding inhalation of A. fumigatus spores, whether individuals should be advised to wear fac

Working paper

Edwards HM, Cogliati M, Kwenda G, Fisher MCet al., 2021, The need for environmental surveillance to understand the ecology, epidemiology and impact of <i>Cryptococcus</i> infection in Africa, FEMS Microbiology Ecology, Vol: 97

<jats:title>ABSTRACT</jats:title> <jats:p>Our understanding of the pathogenic yeasts Cryptococcus neoformans and Cryptococcus gattii has been greatly enhanced by use of genome sequencing technologies. Found ubiquitously as saprotrophs in the environment, inhalation of infectious spores from these pathogens can lead to the disease cryptococcosis. Individuals with compromised immune systems are at particular risk, most notably those living with HIV/AIDS. Genome sequencing in combination with laboratory and clinical studies has revealed diverse lineages with important differences in their observed frequency, virulence and clinical outcomes. However, to date, genomic analyses have focused primarily on clinical isolates that represent only a subset of the diversity in the environment. Enhanced genomic surveillance of these yeasts in their native environments is needed in order to understand their ecology, biology and evolution and how these influence the epidemiology and pathophysiology of clinical disease. This is particularly relevant on the African continent from where global cryptococcal diversity may have originated, yet where environmental sampling and sequencing has been sparse despite harbouring the largest population at risk from cryptococcosis. Here, we review what scientifically and clinically relevant insights have been provided by analysis of environmental Cryptococcus isolates to date and argue that with further sampling, particularly in Africa, many more important discoveries await.</jats:p>

Journal article

Edwards H, Cogliati M, Kwenda G, Fisher Met al., 2021, The need for environmental surveillance to understand the ecology, epidemiology and impact of Cryptococcus infection in Africa, FEMS Microbiology Ecology, Vol: 97, ISSN: 0168-6496

Our understanding of the pathogenic yeasts Cryptococcus neoformans and Cryptococcus gattii has been greatly enhanced by use of genome sequencing technologies. Found ubiquitously as saprotrophs in the environment, inhalation of infectious spores from these pathogens can lead to the disease cryptococcosis. Individuals with compromised immune systems are at particular risk, most notably those living with HIV/AIDS. Genome sequencing in combination with laboratory and clinical studies has revealed diverse lineages with important differences in their observed frequency, virulence and clinical outcomes. However, to date, genomic analyses have focused primarily on clinical isolates that represent only a subset of the diversity in the environment. Enhanced genomic surveillance of these yeasts in their native environments is needed in order to understand their ecology, biology and evolution and how these influence the epidemiology and pathophysiology of clinical disease. This is particularly relevant on the African continent from where global cryptococcal diversity may have originated, yet where environmental sampling and sequencing has been sparse despite harbouring the largest population at risk from cryptococcosis. Here, we review what scientifically and clinically relevant insights have been provided by analysis of environmental Cryptococcus isolates to date and argue that with further sampling, particularly in Africa, many more important discoveries await.

Journal article

Ghosh PN, Verster R, Sewell TR, O'Hanlon SJ, Brookes LM, Rieux A, Wj Garner T, Weldon C, Fisher MCet al., 2021, Discriminating lineages of Batrachochytrium dendrobatidis using quantitative PCR., Molecular Ecology Resources, Vol: 21, Pages: 1452-1459, ISSN: 1471-8278

The ability to detect and monitor infectious disease in a phylogenetically informative manner is critical for their management. Phylogenetically informative diagnostic tests enable patterns of pathogen introduction or changes in the distribution of genotypes to be measured, enabling research into the ecology of the pathogen. Batrachochytrium dendrobatidis (Bd), a causative agent of chytridiomycosis in amphibian populations, emerged worldwide in the 21st century and is composed of six lineages which are display varying levels of virulence in their hosts. Research into the distribution, ecology and pathogenicity of these lineages has been hampered by an inability to type lineage efficiently. Here, we describe a lineage-specific TaqMan qPCR assay that differentiates the two lineages of Bd most commonly associated with chytridiomycosis: BdGPL and BdCAPE. We demonstrate how this assay can be used for the surveillance of wild populations of amphibians in Southern Africa using skin swabs, tissue samples and cultured isolates.

Journal article

Soraggi S, Rhodes J, Altinkaya I, Tarrant O, Balloux F, Fisher MC, Fumagalli Met al., 2021, HMMploidy: inference of ploidy levels from short-read sequencing data

<jats:title>Abstract</jats:title><jats:p>The inference of ploidy levels from genomic data is important to understand molecular mechanisms underpinning genome evolution. However, current methods based on allele frequency and sequencing depth variation do not have power to infer ploidy levels at low- and mid-depth sequencing data, as they do not account for data uncertainty. Here we introduce <jats:monospace>HMMploidy</jats:monospace>, a novel tool that leverages the information from multiple samples and combines the information from sequencing depth and genotype likelihoods. We demonstrate that <jats:monospace>HMMploidy</jats:monospace> outperforms existing methods in most tested scenarios, especially at low-depth with large sample size. We apply <jats:monospace>HMMploidy</jats:monospace> to sequencing data from the pathogenic fungus <jats:italic>Cryptococcus neoformans</jats:italic> and retrieve pervasive patterns of aneuploidy, even when artificially downsampling the sequencing data. We envisage that <jats:monospace>HMMploidy</jats:monospace> will have wide applicability to low-depth sequencing data from polyploid and aneuploid species.</jats:p>

Journal article

Farrer RA, Borman AM, Inkster T, Fisher MC, Johnson EM, Cuomo CAet al., 2021, Genomic epidemiology of a Cryptococcus neoformans case cluster in Glasgow, Scotland, 2018, MICROBIAL GENOMICS, Vol: 7, ISSN: 2057-5858

Journal article

Fisher MC, Murray KA, 2021, Emerging infections and the integrative environment-health sciences: the road ahead, Nature Reviews Microbiology, Vol: 19, Pages: 133-135, ISSN: 1740-1526

The integrative environment-health sciences including One Health, Conservation Medicine, EcoHealth and Planetary Health embody the transdisciplinary synthesis needed to understand the multitude of factors that underpin emerging infections and their management. Future successes in confronting and resolving the complex causal basis of disease emergence to generate robust, systems-oriented risk reduction strategies that preserve both human health as well as promoting sustainable futures represent the ‘Moon Shot’ for the integrative environment-health sciences.

Journal article

Jervis P, Pintanel P, Hopkins K, Wierzbicki C, Shelton J, Skelly E, Rosa G, Almeida-Reinoso D, Eugenia-Ordonez M, Ron S, Harrison X, Fisher Met al., 2021, Post‐epizootic microbiome associations across communities of neotropical amphibians, Molecular Ecology, Vol: 30, Pages: 1322-1335, ISSN: 0962-1083

Microbiome–pathogen interactions are increasingly recognized as an important element of host immunity. While these host‐level interactions will have consequences for community disease dynamics, the factors which influence host microbiomes at larger scales are poorly understood. We here describe landscape‐scale pathogen–microbiome associations within the context of post‐epizootic amphibian chytridiomycosis, a disease caused by the panzootic chytrid fungus Batrachochytrium dendrobatidis. We undertook a survey of Neotropical amphibians across altitudinal gradients in Ecuador ~30 years following the observed amphibian declines and collected skin swab‐samples which were metabarcoded using both fungal (ITS‐2) and bacterial (r16S) amplicons. The data revealed marked variation in patterns of both B. dendrobatidis infection and microbiome structure that are associated with host life history. Stream breeding amphibians were most likely to be infected with B. dendrobatidis. This increased probability of infection was further associated with increased abundance and diversity of non‐Batrachochytrium chytrid fungi in the skin and environmental microbiome. We also show that increased alpha diversity and the relative abundance of fungi are lower in the skin microbiome of adult stream amphibians compared to adult pond‐breeding amphibians, an association not seen for bacteria. Finally, stream tadpoles exhibit lower proportions of predicted protective microbial taxa than pond tadpoles, suggesting reduced biotic resistance. Our analyses show that host breeding ecology strongly shapes pathogen–microbiome associations at a landscape scale, a trait that may influence resilience in the face of emerging infectious diseases.

Journal article

Farthing HN, Jiang J, Henwood AJ, Fenton A, Garner TWJ, Daversa DR, Fisher MC, Montagnes DJSet al., 2021, Microbial grazers may aid in controlling infections caused by the aquatic zoosporic fungus Batrachochytrium dendrobatidis, Frontiers in Microbiology, Vol: 11, ISSN: 1664-302X

Free-living eukaryotic microbes may reduce animal diseases. We evaluated the dynamics by which micrograzers (primarily protozoa) apply top-down control on the chytrid Batrachochytrium dendrobatidis (Bd) a devastating, panzootic pathogen of amphibians. Although micrograzers consumed zoospores (∼3 μm), the dispersal stage of chytrids, not all species grew monoxenically on zoospores. However, the ubiquitous ciliate Tetrahymena pyriformis, which likely co-occurs with Bd, grew at near its maximum rate (r = 1.7 d-1). A functional response (ingestion vs. prey abundance) for T. pyriformis, measured using spore-surrogates (microspheres) revealed maximum ingestion (I max ) of 1.63 × 103 zoospores d-1, with a half saturation constant (k) of 5.75 × 103 zoospores ml-1. Using these growth and grazing data we developed and assessed a population model that incorporated chytrid-host and micrograzer dynamics. Simulations using our data and realistic parameters obtained from the literature suggested that micrograzers could control Bd and potentially prevent chytridiomycosis (defined as 104 sporangia host-1). However, simulated inferior micrograzers (0.7 × I max and 1.5 × k) did not prevent chytridiomycosis, although they ultimately reduced pathogen abundance to below levels resulting in disease. These findings indicate how micrograzer responses can be applied when modeling disease dynamics for Bd and other zoosporic fungi.

Journal article

Fisher MC, Pasmans F, Martel A, 2021, Virulence and Pathogenicity of Chytrid Fungi Causing Amphibian Extinctions, ANNUAL REVIEW OF MICROBIOLOGY, VOL 75, 2021, Vol: 75, Pages: 673-693, ISSN: 0066-4227

Journal article

Verweij PE, Lucas JA, Arendrup MC, Bowyer P, Brinkmann AJF, Denning DW, Dyer PS, Fisher MC, Geenen PL, Gisi U, Hermann D, Hoogendijk A, Kiers E, Lagrou K, Melchers WJG, Rhodes J, Rietveld AG, Schoustra SE, Stenzel K, Zwaan BJ, Fraaije BAet al., 2020, The one health problem of azole resistance in Aspergillus fumigatus: current insights and future research agenda, FUNGAL BIOLOGY REVIEWS, Vol: 34, Pages: 202-214, ISSN: 1749-4613

Journal article

Ghosh P, Brookes L, Edwards H, Fisher M, Jervis P, Kappel D, Sewell T, Shelton J, Skelly E, Rhodes Jet al., 2020, Cross-Disciplinary Genomics Approaches to Studying Emerging Fungal Infections, Life, Vol: 10, ISSN: 2075-1729

Emerging fungal pathogens pose a serious, global and growing threat to food supply systems, wild ecosystems, and human health. However, historic chronic underinvestment in their research has resulted in a limited understanding of their epidemiology relative to bacterial and viral pathogens. Therefore, the untargeted nature of genomics and, more widely, -omics approaches is particularly attractive in addressing the threats posed by and illuminating the biology of these pathogens. Typically, research into plant, human and wildlife mycoses have been largely separated, with limited dialogue between disciplines. However, many serious mycoses facing the world today have common traits irrespective of host species, such as plastic genomes; wide host ranges; large population sizes and an ability to persist outside the host. These commonalities mean that -omics approaches that have been productively applied in one sphere and may also provide important insights in others, where these approaches may have historically been underutilised. In this review, we consider the advances made with genomics approaches in the fields of plant pathology, human medicine and wildlife health and the progress made in linking genomes to other -omics datatypes and sets; we identify the current barriers to linking -omics approaches and how these are being underutilised in each field; and we consider how and which -omics methodologies it is most crucial to build capacity for in the near future.

Journal article

Yu L-S, Rodriguez-Manzano J, Moser N, Moniri A, Malpartida-Cardenas K, Miscourides N, Sewell T, Kochina T, Brackin A, Rhodes J, Holmes AH, Fisher MC, Georgiou Pet al., 2020, Rapid detection of azole-resistant Aspergillus fumigatus in clinical and environmental isolates using lab-on-a-chip diagnostic system, Journal of Clinical Microbiology, Vol: 58, Pages: 1-11, ISSN: 0095-1137

Aspergillus fumigatus has widely evolved resistance to the most commonly used class of antifungal chemicals, the azoles. Current methods for identifying azole resistance are time-consuming and depend on specialized laboratories. There is an urgent need for rapid detection of these emerging pathogens at point-of-care to provide the appropriate treatment in the clinic and to improve management of environmental reservoirs to mitigate the spread of antifungal resistance. Our study demonstrates the rapid and portable detection of the two most relevant genetic markers linked to azole resistance, the mutations TR34 and TR46, found in the promoter region of the gene encoding the azole target, cyp51A. We developed a lab-on-a-chip platform consisting of: (1) tandem-repeat loop-mediated isothermal amplification, (2) state-of-the-art complementary metal-oxide-semiconductor microchip technology for nucleic-acid amplification detection and, (3) and a smartphone application for data acquisition, visualization and cloud connectivity. Specific and sensitive detection was validated with isolates from clinical and environmental samples from 6 countries across 5 continents, showing a lower limit-of-detection of 10 genomic copies per reaction in less than 30 minutes. When fully integrated with a sample preparation module, this diagnostic system will enable the detection of this ubiquitous fungus at the point-of-care, and could help to improve clinical decision making, infection control and epidemiological surveillance.

Journal article

This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.

Request URL: http://wlsprd.imperial.ac.uk:80/respub/WEB-INF/jsp/search-html.jsp Request URI: /respub/WEB-INF/jsp/search-html.jsp Query String: respub-action=search.html&id=00399982&limit=30&person=true