Imperial College London

Professor Matthew Fisher

Faculty of MedicineSchool of Public Health

Professor of Fungal Disease Epidemiology
 
 
 
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Contact

 

+44 (0)20 7594 3787matthew.fisher Website

 
 
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Location

 

VC3Norfolk PlaceSt Mary's Campus

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Summary

 

Publications

Publication Type
Year
to

214 results found

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 JMG, Collins R, Uzzell CB, Alghamdi A, Dyer PS, Singer AC, Fisher MCet al., 2021, Citizen-science surveillance of triazole-resistant Aspergillus fumigatus in UK residential garden soils

<jats:title>Abstract</jats:title><jats:p>Compost is an ecological niche for <jats:italic>Aspergillus fumigatus</jats:italic> 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 <jats:italic>A. fumigatus</jats:italic> 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 <jats:italic>A. fumigatus</jats:italic> 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 <jats:italic>A. fumigatus</jats:italic> 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 <jats:italic>A. fumigatus</jats:italic> lung infections in humans. These isolates were found to contain the common resistance mechanisms in the <jats:italic>A. fumigatus cyp51A</jats:italic> gene TR<jats:sub>34</jats:sub>/L98H or TR<jats:sub>46</jats:sub>/Y121F/T289A, and less common resistance mechanisms TR<jats:sub>34</jats:sub>, TR<jats:sub>53</jats:sub>, TR<jats:sub>46</jats:sub>/Y121F/T289A/S363P/I364V/G448S and (TR<jats:sub>46</jats:sub>)<jats:sup>2</jats:sup>/Y121F/M172I/T289A/G448S. Regression analyses found that soil samples containing compost were significantly more likely to grow susceptible and tebuconazole-resistant <jats:italic>A. fumigatus</jats:italic> than those that did not, and that compost samples grew significant

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, 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

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

<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. <jats:monospace>HMMploidy</jats:monospace> further allows for local inferences of ploidy change to detect within-chromosome variations. 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 polyploidy and 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

Sewell TR, Longcore J, Fisher MC, 2021, Batrachochytrium dendrobatidis., Trends Parasitol

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

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

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

Di Paolo M, Hewitt L, Nwanko 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., JAC Antimicrob Resist, Vol: 3

Background: Individuals with cystic fibrosis (CF) have an increased susceptibility to fungal infection/allergy, with triazoles often used as first-line therapy. Therapeutic drug monitoring (TDM) is essential due to significant pharmacokinetic variability and the recent emergence of triazole resistance worldwide. Objectives: In this retrospective study we analysed the 'real-world' TDM of azole therapy in a large CF cohort, risk factors for subtherapeutic dosing, and the emergence of azole resistance. Methods: All adults with CF on azole therapy in a large single UK centre were included. Clinical demographics, TDM and microbiology were analysed over a 2 year study period (2015-17) with multivariate logistic regression used to identify risk factors for subtherapeutic dosing. Results: 91 adults were treated with azole medication during the study period. A high prevalence of chronic subtherapeutic azole dosing was seen with voriconazole (60.8%) and itraconazole capsule (59.6%) use, representing significant risk factors for subtherapeutic levels. Rapid emergence of azole resistance was additionally seen over the follow-up period with a 21.4% probability of CF patients developing a resistant fungal isolate after 2 years. No significant relationship was found however between subtherapeutic azole dosing and azole resistance emergence. Conclusions: Our study demonstrates a high prevalence of subtherapeutic azole levels in CF adults with increased risk using itraconazole capsules and voriconazole therapy. We show rapid emergence of azole resistance highlighting the need for effective antifungal stewardship. Further large longitudinal studies are needed to understand the effects of antifungal resistance on outcome in CF and the implications of subtherapeutic dosing on resistance evolution.

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

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

Armstrong-James D, Youngs J, Bicanic T, Abdolrasouli A, Denning DW, Johnson E, Mehra V, Pagliuca T, Patel B, Rhodes J, Schelenz S, Shah A, van de Veerdonk FL, Verweij PE, White PL, Fisher MCet al., 2020, Confronting and mitigating the risk of COVID-19 Associated Pulmonary Aspergillosis (CAPA), European Respiratory Journal, Vol: 56, Pages: 1-10, ISSN: 0903-1936

Cases of COVID-19 associated pulmonary aspergillosis (CAPA) are being increasingly reported and physicians treating patients with COVID-19-related lung disease need to actively consider these fungal co-infections.The SARS-CoV-2 (COVID-19) virus causes a wide spectrum of disease in healthy individuals as well as those with common comorbidities [1]. Severe COVID-19 is characterised acute respiratory distress syndrome (ARDS) secondary to viral pneumonitis, treatment of which may require mechanical ventilation or extracorporeal membrane oxygenation (ECMO) [2]. Clinicians are alert to the possibility of bacterial co-infection as a complication of lower respiratory tract viral infection; for example a recent review found that 72% of patients with COVID-19 received antimicrobial therapy [3]. However, the risk of fungal co-infection, in particular COVID-19 associated pulmonary aspergillosis (CAPA), remains underappreciated.Fungal disease consistent with invasive aspergillosis (IA) has been observed with other severe Coronaviruses such as Severe Acute Respiratory Syndrome (SARS-CoV-2003) [4, 5] and Middle East Respiratory Syndrome (MERS-CoV) [6]. From the outset of the COVID-19 pandemic, there were warning signs of secondary invasive fungal infection; Aspergillus flavus was isolated from the respiratory tract from one of 99 patients in the first COVID-19 cohort from Wuhan to be reported in any detail [2] and Aspergillus spp. were isolated from 2/52 (3.8%) of a subsequent cohort of critically unwell patients from this region [7]. More recently, retrospective case series from Belgium [8], France [9], The Netherlands [10] and Germany [11] have reported evidence of CAPA in an alarming 20–35% of mechanically ventilated patients.

Journal article

Shelton J, Fisher M, Singer A, 2020, Campaign-based citizen science for environmental mycology: the science solstice and summer soil-stice projects to assess drug resistance in air- and soil-borne Aspergillus fumigatus, Citizen Science: Theory and Practice, Vol: 5, Pages: 1-13, ISSN: 2057-4991

Citizen science projects are often undertaken for ecological and environmental research purposes but also have great potential for use in microbiology research to track the emergence and spread of pathogens in the environment. Science Solstice and Summer Soil-stice are mycology citizen science projects aimed at collecting air and soil samples, respectively, in the United Kingdom (UK), that will be used to culture Aspergillus fumigatus fungal spores and to determine their drug resistance. A. fumigatus plays an important role in the environment as a decomposer of plant material, but is also a human lung pathogen. Infection with drug-resistant spores can lead to a worse clinical outcome for the patient.On the four solstice and equinox days between June 2018 and March 2019, volunteers were asked to collect air samples from their homes and workplaces and return them to our lab in Freepost envelopes (UK only) or were reimbursed for postage if returning samples from outside of the UK. An additional round of samples was requested from UK volunteers’ gardens and/or compost on the June 2019 solstice. In total, 787 volunteers returned 2,132 air samples and 509 soil samples, which grew a total of 7,991 A. fumigatus colonies. The estimated total cost of the study was £2,650, the equivalent of £0.33 per A. fumigatus colony grown.Incorporating citizen science into the environmental surveillance of drug-resistant A. fumigatus allowed for the simultaneous collection of hundreds of environmental samples across the entire UK on the same day. The insights generated from this study would not be practical in the absence of public participation, which offers opportunities to ask scientific questions that were previously un-askable.

Journal article

Rodrigues AM, Beale MA, Hagen F, Fisher MC, Terra PPD, de Hoog S, Brilhante RSN, de Aguiar Cordeiro R, de Souza Collares Maia Castelo-Branco D, Rocha MFG, Sidrim JJC, de Camargo ZPet al., 2020, The global epidemiology of emerging Histoplasma species in recent years, Studies in Mycology, Vol: 97, ISSN: 0166-0616

Histoplasmosis is a serious infectious disease in humans caused by Histoplasma spp. (Onygenales), whose natural reservoirs are thought to be soil enriched with bird and bat guano. The true global burden of histoplasmosis is underestimated and frequently the pulmonary manifestations are misdiagnosed as tuberculosis. Molecular data on epidemiology of Histoplasma are still scarce, even though there is increasing recognition of histoplasmosis in recent years in areas distant from the traditional endemic regions in the Americas. We used multi-locus sequence data from protein coding loci (ADP-ribosylation factor, H antigen precursor, and delta-9 fatty acid desaturase), DNA barcoding (ITS1/2+5.8s), AFLP markers and mating type analysis to determine the genetic diversity, population structure and recognise the existence of different phylogenetic species among 436 isolates of Histoplasma obtained globally. Our study describes new phylogenetic species and the molecular characteristics of Histoplasma lineages causing outbreaks with a high number of severe outcomes in Northeast Brazil between 2011 and 2015. Genetic diversity levels provide evidence for recombination, common ancestry and clustering of Brazilian isolates at different geographic scales with the emergence of LAm C, a new genotype assigned to a separate population cluster in Northeast Brazil that exhibited low diversity indicative of isolation. The global survey revealed that the high genetic variability among Brazilian isolates along with the presence of divergent cryptic species and/or genotypes may support the hypothesis of Brazil being the center of dispersion of Histoplasma in South America, possibly with the contribution of migratory hosts such as birds and bats. Outside Brazil, the predominant species depends on the region. We confirm that histoplasmosis has significantly broadened its area of occurrence, an important feature of emerging pathogens. From a practical point of view, our data point to the emergen

Journal article

Brackin AP, Shelton JMG, Abdolrasouli A, Fisher MC, Sewell TRet al., 2020, A low-cost tebuconazole-based screening test for azole-resistant aspergillus fumigatus., Current protocols in microbiology, Vol: 58, Pages: 1-12, ISSN: 1934-8525

The global emergence of azole resistance in Aspergillus fumigatus is resulting in health and food security concerns. Rapid diagnostics and environmental surveillance methods are key to understanding the distribution and prevalence of azole resistance. However, such methods are often associated with high costs and are not always applicable to laboratories based in the least-developed countries. Here, we present and validate a low-cost screening protocol that can be used to differentiate between azole-susceptible "wild-type" and azole-resistant A. fumigatus isolates. © 2020 The Authors. Basic Protocol 1: Preparation of Tebucheck multi-well plates Basic Protocol 2: Inoculation of Tebucheck multi-well plates.

Journal article

Ghosh PN, Verster R, Sewell T, OHanlon S, Brookes LM, Rieux A, Garner TWJ, Weldon C, Fisher MCet al., 2020, Discriminating Lineages of Batrachochytrium dendrobatidis using quantitative PCR, Publisher: Cold Spring Harbor Laboratory

<jats:title>Abstract</jats:title><jats:p>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. <jats:italic>Batrachochytrium dendrobatidis</jats:italic> (<jats:italic>Bd</jats:italic>), a causative agent of chytridiomycosis in amphibian populations, emerged worldwide in the 21<jats:sup>st</jats:sup> century and is composed of six lineages which are display varying levels of virulence in their hosts.</jats:p><jats:p>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 <jats:italic>Bd</jats:italic> most commonly associated with chytridiomycosis: <jats:italic>Bd</jats:italic>GPL and <jats:italic>Bd</jats:italic>CAPE. 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.</jats:p>

Working paper

Jervis P, Karlsdottir B, Jehle R, Almeida-Reinoso D, Almeida-Reinoso F, Ron S, Fisher MC, Merino-Viteri Aet al., 2020, Disease reservoirs threaten the recently rediscovered Podocarpus Stubfoot Toad (Atelopus podocarpus), Amphibian and Reptile Conservation, Vol: 14, Pages: 157-164, ISSN: 1083-446X

The Andes have experienced an unprecedented wave of amphibian declines and extinctions thatare linked to a combination of habitat reduction and the spread of the fungal pathogen, Batrachochytriumdendrobatidis (Bd). In the present study, a range of high-altitude habitats in Southern Ecuador were surveyedfor the presence of Bd. With a particular focus on Yacuri National Park, infection data are presented fromacross the resident amphibian community. This community contains a once putatively extinct species whichwas rediscovered in 2016, the Podocarpus Stubfoot Toad (Atelopus podocarpus). Across species, local Bdprevalence was 73% in tadpoles (n = 41 individuals from three species) and 14% in adults (n = 43 individualsfrom 14 species). Strikingly, 93% (14/15) of tested tadpoles of the recently described local endemic, Gastrothecayacuri, were infected with a high pathogen load, suggesting that this species likely acts as a reservoir ofinfection in Yacuri. These fndings show that the threat of disease for A. podocarpus still exists, and that thisspecies requires urgent action to ensure its survival.

Journal article

de Carvalho JA, Hagen F, Fisher MC, de Camargo ZP, Rodrigues AMet al., 2020, Genome-wide mapping using new AFLP markers to explore intraspecific variation among pathogenic Sporothrix species, PLOS NEGLECTED TROPICAL DISEASES, Vol: 14, ISSN: 1935-2735

Journal article

Shelton JMG, Fisher MC, Singer AC, 2020, Campaign-Based Citizen Science for Environmental Mycology: the “Science Solstice” and “Summer Soil-stice” Projects to Assess Drug Resistance in Air and Soilborne Aspergillus fumigatus, Publisher: Cold Spring Harbor Laboratory

<jats:title>Abstract</jats:title><jats:p>Citizen science projects are often undertaken for ecological and environmental research purposes but also have great potential for use in microbiology research to track the emergence and spread of pathogens in the environment. ‘Science Solstice’ and ‘Summer Soil-stice’ are mycology citizen science projects aimed at assessing drug resistance in <jats:italic>Aspergillus fumigatus</jats:italic> fungal spores found in air and soil, respectively, in the United Kingdom (UK). <jats:italic>A. fumigatus</jats:italic> plays an important role in the environment as a decomposer of plant material, but is also an opportunistic human lung pathogen. Infection with drug-resistant spores can lead to a worse clinical outcome for the patient.</jats:p><jats:p>On the first four solstice and equinox days between June 2018 and June 2019, volunteers were asked to collect air samples from their homes and workplaces and return them to our lab in Freepost envelopes. An additional round of samples was requested from volunteer’s gardens and/or compost on the June 2019 solstice. In total, 787 volunteers returned 2,132 air samples and 509 soil samples, which grew a total of 7,991 <jats:italic>A. fumigatus</jats:italic> colonies. The estimated total cost of the study was £2,650; the equivalent of 33 pence per <jats:italic>A. fumigatus</jats:italic> colony grown.</jats:p><jats:p>Incorporating citizen science into the environmental surveillance of drug-resistant <jats:italic>A. fumigatus</jats:italic> allowed for the simultaneous collection of hundreds of environmental samples across the entire UK on the same day. The insights generated from this study would not be practical in the absence of public participation and offers opportunities to ask scientific questions that were previously unaskable.</jats:p>

Working paper

Fisher MC, Garner TWJ, 2020, Chytrid fungi and global amphibian declines, Nature Reviews Microbiology, Vol: 18, Pages: 332-343, ISSN: 1740-1526

Discovering that chytrid fungi cause chytridiomycosis in amphibians represented a paradigm shift in our understanding of how emerging infectious diseases contribute to global patterns of biodiversity loss. In this Review we describe how the use of multidisciplinary biological approaches has been essential to pinpointing the origins of amphibian-parasitizing chytrid fungi, including Batrachochytrium dendrobatidis and Batrachochytrium salamandrivorans, as well as to timing their emergence, tracking their cycles of expansion and identifying the core mechanisms that underpin their pathogenicity. We discuss the development of the experimental methods and bioinformatics toolkits that have provided a fuller understanding of batrachochytrid biology and informed policy and control measures.

Journal article

Doherty-Bone TM, Cunningham AA, Fisher MC, Garner TWJ, Ghosh P, Gower DJ, Verster R, Weldon Cet al., 2020, Amphibian chytrid fungus in Africa - realigning hypotheses and the research paradigm, Animal Conservation, Vol: 23, Pages: 239-244, ISSN: 1367-9430

The amphibian chytrid fungus Batrachochytrium dendrobatidis (Bd), responsible for numerous amphibian declines and extinctions, was previously thought to originate from the African continent. This was based on infected museum specimens from early 20th century South Africa, Cameroon and Uganda. Further research on archived specimens from other continents eventually revealed early 20th century records also in Brazil and Japan. Recent robust analysis of genomic diversity and phylogeny of Bd has shown origin from Asia to be more plausible. This raises the issue that the threat of Bd for African amphibians as a novel pathogen has been underestimated. There are now cases where dramatic amphibian declines in disparate mountains on the continent could be attributed to Bd, and this necessitates an urgent realigning of hypotheses and the research agenda for amphibian conservation on the continent. Notably, hotspots of amphibian host naivety include West Africa where this pathogen has so far not been detected. We discuss research gaps that amphibian conservationists might focus on, notably more genomic sequencing of the BdCAPE (the less virulent) lineage to determine its date of emergence, and assessing the susceptibility of different amphibian species to infection, disease and decline to better prioritize conservation actions.

Journal article

Fisher MC, Gurr SJ, Cuomo CA, Blehert DS, Jin H, Stukenbrock EH, Stajich JE, Kahmann R, Boone C, Denning DW, Gow NAR, Klein BS, Kronstad JW, Sheppard DC, Taylor JW, Wright GD, Heitman J, Casadevall A, Cowen LEet al., 2020, Threats Posed by the Fungal Kingdom to Humans, Wildlife, and Agriculture, MBIO, Vol: 11, ISSN: 2150-7511

Journal article

Scheele BC, Pasmans F, Skerratt LF, Berger L, Martel A, Beukema W, Acevedo AA, Burrowes PA, Carvalho T, Catenazzi A, De la Riva I, Fisher MC, Flechas SV, Foster CN, Frias-Alvarez P, Garner TWJ, Gratwicke B, Guayasamin JM, Hirschfeld M, Kolby JE, Kosch TA, La Marca E, Lindenmayer DB, Lips KR, Longo AV, Maneyro R, McDonald CA, Mendelson J, Palacios-Rodriguez P, Parra-Olea G, Richards-Zawacki CL, Roedel M-O, Rovito SM, Soto-Azat C, Toledo LF, Voyles J, Weldon C, Whitfield SM, Wilkinson M, Zamudio KR, Canessa Set al., 2020, Response to Comment on "Amphibian fungal panzootic causes catastrophic and ongoing loss of biodiversity", SCIENCE, Vol: 367, ISSN: 0036-8075

Journal article

Harrison XA, Sewell T, Fisher M, Antwis REet al., 2020, Designing probiotic therapies with broad-spectrum activity against a wildlife pathogen, Frontiers in Microbiology, Vol: 10, Pages: 1-11, ISSN: 1664-302X

Host-associated microbes form an important component of immunity that protect against infection by pathogens. Treating wild individuals with these protective microbes, known as probiotics, can reduce rates of infection and disease in both wild and captive settings. However, the utility of probiotics for tackling wildlife disease requires that they offer consistent protection across the broad genomic variation of the pathogen that hosts can encounter in natural settings. Here we develop multi-isolate probiotic consortia with the aim of effecting broad-spectrum inhibition of growth of the lethal amphibian pathogen Batrachochytrium dendrobatidis (Bd) when tested against nine Bd isolates from two distinct lineages. Though we achieved strong growth inhibition between 70 and 100% for seven Bd isolates, two isolates appeared consistently resistant to inhibition, irrespective of probiotic strategy employed. We found no evidence that genomic relatedness of the chytrid predicted similarity of inhibition scores, nor that increasing the genetic diversity of the bacterial consortia could offer stronger inhibition of pathogen growth, even for the two resistant isolates. Our findings have important consequences for the application of probiotics to mitigate wildlife diseases in the face of extensive pathogen genomic variation.

Journal article

Georgiou P, Yu L-S, Malpartida-Cardenas K, Fisher M, Moser N, Rodriguez Manzano Jet al., 2019, Method for detecting a tandem repeat, WO2019234252A1

The present application relates to methods for detecting a tandem repeat in a nucleic acid sequence under isothermal conditions using primers.

Patent

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