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

206 results found

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

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., Microb Genom, Vol: 7

In 2018, a cluster of two cases of cryptococcosis occurred at the Queen Elizabeth University Hospital (QEUH) in Glasgow, Scotland (UK). It was postulated that these cases may have been linked to pigeon droppings found on the hospital site, given there have been previous reports of Cryptococcus neoformans associated with pigeon guano. Although some samples of pigeon guano taken from the site yielded culturable yeast from genera related to Cryptococcus, they have since been classified as Naganishia or Papiliotrema spp., and no isolates of C. neoformans were recovered from either the guano or subsequent widespread air sampling. In an attempt to further elucidate any possible shared source of the clinical isolates, we used whole-genome sequencing and phylogenetic analysis to examine the relationship of the two Cryptococcus isolates from the QEUH cases, along with two isolates from sporadic cases treated at a different Glasgow hospital earlier in 2018. Our work demonstrated that these four clinical isolates were not clonally related; while all isolates were from the VNI global lineage and of the same mating type (MATα), the genotypes of the two QEUH isolates were separated by 1885 base changes and belonged to different sub-lineages, recently described as the intercontinental sub-clades VNIa-93 and VNIa-5. In contrast, one of the two sporadic 2018 clinical isolates was determined to belong to the VNIb sub-lineage and the other classified as a VNIV/VNI hybrid. Our work demonstrated that the two 2018 QEUH isolates and the two prior C. neoformans clinical isolates were all genetically distinct. It was not possible to determine whether the QEUH genotypes stemmed from independent sources or from the same source, i.e. pigeons carrying different genotypes, but it should be noted that whilst members of allied genera within the Tremellomycetes were isolated from the hospital environment, there were no environmental isolations of C. neoformans.

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

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-Antimicrobial Resistance, Vol: 3

<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>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.</jats:p> </jats:sec> <jats:sec> <jats:title>Objectives</jats:title> <jats:p>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.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>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.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>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 a

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

Ghosh PN, Verster R, Sewell TR, O'Hanlon SJ, Brookes LM, Rieux A, Wj Garner T, Weldon C, Fisher MCet al., 2020, Discriminating lineages of Batrachochytrium dendrobatidis using quantitative PCR., Molecular Ecology Resources, 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

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

Rhodes J, Fisher MC, 2019, Global epidemiology of emerging Candida auris, Current Opinion in Microbiology, Vol: 52, Pages: 84-89, ISSN: 1369-5274

The discovery in 2009 of a new species of yeast, Candida auris, heralded the arrival of a novel emerging human infectious disease. This review highlights the unique characteristics of C. auris that have lled to it being of public health concern worldwide, namely public health concern, namely its global emergence, its ability to cause nosocomial outbreaks in healthcare settings, its innate and emerging resistance to multiple antifungal drugs and its resilience in the face of hygiene and infection control measures. Genomic epidemiology has identified four emergences of C. auris marked by four clades of the pathogen. These clades of C. auris are genetically dissimilar and are associated with differential resistance to antifungal drugs, suggesting that they will continue to phenotypically diverge into the future. The global emergence of C. auris testifies to the unmapped nature of Kingdom Fungi, and represents a new nosocomial threat that will require enhanced infection control across diverse healthcare and community settings.

Journal article

Farrer RA, Chang M, Davis MJ, van Dorp L, Yang D-H, Shea T, Sewell TR, Meyer W, Balloux F, Edwards HM, Chanda D, Kwenda G, Vanhove M, Chang YC, Cuomo CA, Fisher MC, Kwon-Chung KJet al., 2019, A new lineage of cryptococcus gattii (VGV) discovered in the Central Zambezian Miombo Woodlands, mBio, Vol: 10, Pages: 1-19, ISSN: 2150-7511

We discovered a new lineage of the globally important fungal pathogen Cryptococcus gattii on the basis of analysis of six isolates collected from three locations spanning the Central Miombo Woodlands of Zambia, Africa. All isolates were from environments (middens and tree holes) that are associated with a small mammal, the African hyrax. Phylogenetic and population genetic analyses confirmed that these isolates form a distinct, deeply divergent lineage, which we name VGV. VGV comprises two subclades (A and B) that are capable of causing mild lung infection with negligible neurotropism in mice. Comparing the VGV genome to previously identified lineages of C. gattii revealed a unique suite of genes together with gene loss and inversion events. However, standard URA5 restriction fragment length polymorphism (RFLP) analysis could not distinguish between VGV and VGIV isolates. We therefore developed a new URA5 RFLP method that can reliably identify the newly described lineage. Our work highlights how sampling understudied ecological regions alongside genomic and functional characterization can broaden our understanding of the evolution and ecology of major global pathogens.

Journal article

Bates KA, Shelton JMG, Mercier VL, Hopkins KP, Harrison XA, Petrovan SO, Fisher MCet al., 2019, Captivity and infection by the fungal pathogen batrachochytrium salamandrivorans perturb the amphibian skin microbiome, Frontiers in Microbiology, Vol: 10, ISSN: 1664-302X

The emerging fungal pathogen, Batrachochytrium salamandrivorans (Bsal) is responsible for the catastrophic decline of European salamanders and poses a threat to amphibians globally. The amphibian skin microbiome can influence disease outcome for several host-pathogen systems, yet little is known of its role in Bsal infection. In addition, many experimental in-vivo amphibian disease studies to date have relied on specimens that have been kept in captivity for long periods without considering the influence of environment on the microbiome and how this may impact the host response to pathogen exposure. We characterized the impact of captivity and exposure to Bsal on the skin bacterial and fungal communities of two co-occurring European newt species, the smooth newt, Lissotriton vulgaris and the great-crested newt, Triturus cristatus. We show that captivity led to significant losses in bacterial and fungal diversity of amphibian skin, which may be indicative of a decline in microbe-mediated protection. We further demonstrate that in both L. vulgaris and T. cristatus, Bsal infection was associated with changes in the composition of skin bacterial communities with possible negative consequences to host health. Our findings advance current understanding of the role of host-associated microbiota in Bsal infection and highlight important considerations for ex-situ amphibian conservation programmes.

Journal article

Sewell TR, Zhang Y, Brackin AP, Shelton JMG, Rhodes J, Fisher MC, Sewell Tet al., 2019, Elevated prevalence of azole resistant Aspergillus fumigatus in urban versus rural environments in the United Kingdom., Antimicrob Agents Chemother

Azole resistance in the opportunistic pathogen Aspergillus fumigatus is increasing, dominated primarily by two environmentally-associated resistance alleles: TR34/L98H and TR46/Y121F/T289A. By sampling soils across the South of England we assess the prevalence of azole resistant A. fumigatus (ARAf) in samples collected in both urban and rural locations. We characterise the susceptibility profiles of the resistant isolates to three medical azoles, identify the underlying genetic basis of resistance and investigate their genetic relationships. ARAf was detected in 6.7% of the soil samples, with a higher prevalence in urban (13.8%) compared to rural (1.1%) locations. Twenty isolates were confirmed to exhibit clinical breakpoints for resistance to at least one of three medical azoles, with 18 isolates exhibiting resistance to itraconazole, six to voriconazole and two showing elevated minimum inhibitory concentration to posaconazole. Thirteen of the resistant isolates harboured the TR34/L98H resistance allele and six isolates carried the TR46/Y121F/T289A allele. The 20 azole-resistant isolates were spread across five csp1 genetic subtypes, t01, t02, t04B, t09 and t18 with t02 the predominant subtype. Our study demonstrates that ARAf can be easily isolated in the South of England, especially in urban city centres, which appear to play an important role in the epidemiology of environmentally-linked drug resistant A. fumigatus.

Journal article

Sewell T, Zhu J, Rhodes J, Hagen F, Mels JF, Fisher M, Jombart Tet al., 2019, Non-random distribution of azole resistance across the global population of Aspergillus fumigatus, mBio, Vol: 10, ISSN: 2150-7511

The emergence of azole resistance in the pathogenic fungus Aspergillus fumigatus has continued to increase, with the dominant resistance mechanisms, consisting of a 34-nucleotide tandem repeat (TR34)/L98H and TR46/Y121F/T289A, now showing a structured global distribution. Using hierarchical clustering and multivariate analysis of 4,049 A. fumigatus isolates collected worldwide and genotyped at nine microsatellite loci using analysis of short tandem repeats of A. fumigatus (STRAf), we show that A. fumigatus can be subdivided into two broad clades and that cyp51A alleles TR34/L98H and TR46/Y121F/T289A are unevenly distributed across these two populations. Diversity indices show that azole-resistant isolates are genetically depauperate compared to their wild-type counterparts, compatible with selective sweeps accompanying the selection of beneficial mutations. Strikingly, we found that azole-resistant clones with identical microsatellite profiles were globally distributed and sourced from both clinical and environmental locations, confirming that azole resistance is an international public health concern. Our work provides a framework for the analysis of A. fumigatus isolates based on their microsatellite profile, which we have incorporated into a freely available, user-friendly R Shiny application (AfumID) that provides clinicians and researchers with a method for the fast, automated characterization of A. fumigatus genetic relatedness. Our study highlights the effect that azole drug resistance is having on the genetic diversity of A. fumigatus and emphasizes its global importance upon this medically important pathogenic fungus.IMPORTANCE Azole drug resistance in the human-pathogenic fungus Aspergillus fumigatus continues to emerge, potentially leading to untreatable aspergillosis in immunosuppressed hosts. Two dominant, environmentally associated resistance mechanisms, which are thought to have evolved through selection by the agricultural application of azole fungic

Journal article

Sewell TR, Zhang Y, Brackin AP, Shelton JMG, Rhodes J, Fisher MCet al., 2019, Elevated prevalence of azole resistant Aspergillus fumigatus in urban versus rural environments in the United Kingdom, Publisher: Cold Spring Harbor Laboratory

<jats:title>Abstract</jats:title><jats:p>Azole resistance in the opportunistic pathogen <jats:italic>Aspergillus fumigatus</jats:italic> is increasing, dominated primarily by two environmentally-associated resistance alleles: TR<jats:sub>34</jats:sub>/L98H and TR<jats:sub>46</jats:sub>/Y121F/T289A. Using an environmental sampling strategy across the South of England we assess the prevalence of azole resistant <jats:italic>A. fumigatus</jats:italic> (AR<jats:italic>Af</jats:italic>) in soil samples collected in both urban and rural locations. We characterise the susceptibility profiles of the resistant isolates to three medical azoles, identify the underlying genetic basis of resistance and investigate their genetic relationships. AR<jats:italic>Af</jats:italic> was detected in 6.7% of the soil samples, with a higher prevalence in urban (13.8%) compared to rural (1.1%) locations. Nineteen isolates were confirmed to exhibit clinical breakpoints for resistance to at least one of three medical azoles, with 18 isolates exhibiting resistance to itraconazole, four to voriconazole, with two also showing additional elevated minimum inhibitory concentration to posaconazole. Thirteen of the resistant isolates harboured the TR<jats:sub>34</jats:sub>/L98H resistance allele and six isolates carried TR<jats:sub>46</jats:sub>/Y121F/T289A allele. The 19 azole-resistant isolates were spread across five <jats:italic>csp1</jats:italic> genetic subtypes, t01, t02, t04B, t09 and t18 with t02 the predominant subtype. Our study demonstrates that AR<jats:italic>Af</jats:italic> can be easily isolated in the South of England, especially in urban city centres, which appear to play an important role in the epidemiology of environmentally-linked drug resistant <jats:italic>A. fumigatus</jats:italic>.</jats:p>

Working paper

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, Frías-Álvarez 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, Rödel M-O, Rovito SM, Soto-Azat C, Toledo LF, Voyles J, Weldon C, Whitfield SM, Wilkinson M, Zamudio KR, Canessa Set al., 2019, Amphibian fungal panzootic causes catastrophic and ongoing loss of biodiversity, Science, Vol: 363, Pages: 1459-1463, ISSN: 0036-8075

Anthropogenic trade and development have broken down dispersal barriers, facilitating the spread of diseases that threaten Earth's biodiversity. We present a global, quantitative assessment of the amphibian chytridiomycosis panzootic, one of the most impactful examples of disease spread, and demonstrate its role in the decline of at least 501 amphibian species over the past half-century, including 90 presumed extinctions. The effects of chytridiomycosis have been greatest in large-bodied, range-restricted anurans in wet climates in the Americas and Australia. Declines peaked in the 1980s, and only 12% of declined species show signs of recovery, whereas 39% are experiencing ongoing decline. There is risk of further chytridiomycosis outbreaks in new areas. The chytridiomycosis panzootic represents the greatest recorded loss of biodiversity attributable to a disease.

Journal article

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