Publications
235 results found
Fisher MCC, Denning DWW, 2023, The WHO fungal priority pathogens list as a game-changer, NATURE REVIEWS MICROBIOLOGY, ISSN: 1740-1526
Wacker T, Helmstetter N, Wilson D, et al., 2023, Two-speed genome evolution drives pathogenicity in fungal pathogens of animals., Proc Natl Acad Sci U S A, Vol: 120
The origins and evolution of virulence in amphibian-infecting chytrids Batrachochytrium dendrobatidis (Bd) and Batrachochytrium salamandrivorans (Bsal) are largely unknown. Here, we use deep nanopore sequencing of Bsal and comparative genomics against 21 high-quality genome assemblies that span the fungal Chytridiomycota. We discover that Bsal has the most repeat-rich genome of the Chytridiomycota, comprising 40.9% repetitive elements; this genome has expanded to more than 3× the length of its conspecific Bd, with autonomous and fully functional LTR/Gypsy elements contributing significantly to the expansion. The M36 metalloprotease virulence factors are highly expanded (n = 177) in Bsal, most of which (53%) are flanked by transposable elements, suggesting they have a repeat-associated expansion. We find enrichment upstream of M36 metalloprotease genes of three novel repeat families belonging to the repeat superfamily of LINEs that are implicated with gene copy number variations. Additionally, Bsal has a highly compartmentalized genome architecture, with virulence factors enriched in gene-sparse/repeat-rich compartments, while core conserved genes are enriched in gene-rich/repeat-poor compartments. Genes upregulated during infection are primarily found in the gene-sparse/repeat-rich compartment in both Bd and Bsal. Furthermore, genes with signatures of positive selection in Bd are enriched in repeat-rich regions, suggesting these regions are a cradle for the evolution of chytrid pathogenicity. These are the hallmarks of two-speed genome evolution, and this study provides evidence of two-speed genomes in an animal pathogen, shedding light on the evolution of fungal pathogens of vertebrates driving global declines and extinctions.
Winter DJ, Weir BS, Glare T, et al., 2022, A single fungal strain was the unexpected cause of a mass aspergillosis outbreak in the world's largest and only flightless parrot., iScience, Vol: 25, Pages: 105470-105470, ISSN: 2589-0042
Kākāpō are a critically endangered species of parrots restricted to a few islands off the coast of New Zealand. Kākāpō are very closely monitored, especially during nesting seasons. In 2019, during a highly successful nesting season, an outbreak of aspergillosis affected 21 individuals and led to the deaths of 9, leaving a population of only 211 kākāpō. In monitoring this outbreak, cultures of aspergillus were grown, and genome sequenced. These sequences demonstrate that, very unusually for an aspergillus outbreak, a single strain of aspergillus caused the outbreak. This strain was found on two islands, but only one had an outbreak of aspergillosis; indicating that the strain was necessary, but not sufficient, to cause disease. Our analysis provides an understanding of the 2019 outbreak and provides potential ways to manage such events in the future.
Schmeller DS, Urbach D, Bates K, et al., 2022, Scientists' warning of threats to mountains, SCIENCE OF THE TOTAL ENVIRONMENT, Vol: 853, ISSN: 0048-9697
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Schmeller DS, Cheng T, Shelton J, et al., 2022, Environment is associated with chytrid infection and skin microbiome richness on an amphibian rich island (Taiwan), Scientific Reports, Vol: 12, ISSN: 2045-2322
Growing evidence suggests that the origins of the panzootic amphibian pathogens Batrachochytrium dendrobatidis (Bd) and Batrachochytrium salamandrivorans (Bsal) are in Asia. In Taiwan, an island hotspot of high amphibian diversity, no amphibian mass mortality events linked to Bd or Bsal have been reported. We conducted a multi-year study across this subtropical island, sampling 2517 individuals from 30 species at 34 field sites, between 2010 and 2017, and including 171 museum samples collected between 1981 and 2009. We analyzed the skin microbiome of 153 samples (6 species) from 2017 in order to assess any association between the amphibian skin microbiome and the probability of infection amongst different host species. We did not detect Bsal in our samples, but found widespread infection by Bd across central and northern Taiwan, both taxonomically and spatially. Museum samples show that Bd has been present in Taiwan since at least 1990. Host species, geography (elevation), climatic conditions and microbial richness were all associated with the prevalence of infection. Host life-history traits, skin microbiome composition and phylogeny were associated with lower prevalence of infection for high altitude species. Overall, we observed low prevalence and burden of infection in host populations, suggesting that Bd is enzootic in Taiwan where it causes subclinical infections. While amphibian species in Taiwan are currently threatened by habitat loss, our study indicates that Bd is in an endemic equilibrium with the populations and species we investigated. However, ongoing surveillance of the infection is warranted, as changing environmental conditions may disturb the currently stable equilibrium.
Case NT, Berman J, Blehert DS, et al., 2022, The future of fungi: threats and opportunities, G3-GENES GENOMES GENETICS, Vol: 12, ISSN: 2160-1836
Rhodes J, Abdolrasouli A, Dunne K, et al., 2022, Population genomics confirms acquisition of drug-resistant Aspergillus fumigatus infection by humans from the environment (vol 7, pg 663, 2022), NATURE MICROBIOLOGY, Vol: 7, Pages: 1944-1944, ISSN: 2058-5276
Furukawa T, van Rhijn N, Chown H, et 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
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.
Fisher MC, Alastruey-Izquierdo A, Berman J, et al., 2022, Tackling the emerging threat of antifungal resistance to human health, NATURE REVIEWS MICROBIOLOGY, Vol: 20, Pages: 557-571, ISSN: 1740-1526
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Furukawa T, van Rhijn N, Chown H, et 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>
Bates KA, Sommer U, Hopkins KP, et 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
Shelton J, Collins R, Uzzell CB, et 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
Duong T-MN, Le T-V, Tran K-LH, et 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).
Bosch J, Thumsová B, López-Rojo N, et 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.
Wacker T, Helmstetter N, Wilson D, et 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>
Rocchi S, Sewell TR, Valot B, et 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.
Alvarado-Rybak M, Acuña P, Peñafiel-Ricaurte A, et 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.
Sewell TR, Longcore J, Fisher MC, 2021, Batrachochytrium dendrobatidis, TRENDS IN PARASITOLOGY, Vol: 37, Pages: 933-934, ISSN: 1471-4922
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Brackin A, Hemmings S, Fisher M, et 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.
Di Paolo M, Hewitt L, Nwankwo E, et 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
de Carvalho JA, Beale MA, Hagen F, et al., 2021, Trends in the molecular epidemiology and population genetics of emerging Sporothrix species, STUDIES IN MYCOLOGY, ISSN: 0166-0616
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Roberto TN, de Carvalho JA, Beale MA, et 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
Di Paolo M, Hewitt L, Nwankwo E, et 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.].
Shelton J, Collins R, Uzzell C, et 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
Edwards HM, Cogliati M, Kwenda G, et 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>
Edwards H, Cogliati M, Kwenda G, et 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.
Ghosh PN, Verster R, Sewell TR, et 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.
Farrer RA, Borman AM, Inkster T, et al., 2021, Genomic epidemiology of a Cryptococcus neoformans case cluster in Glasgow, Scotland, 2018, MICROBIAL GENOMICS, Vol: 7, ISSN: 2057-5858
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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.
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