Tackling emerging fungal threats to animal health, food security and ecosystem resilience

09:05-09:30 A plague on frogs...

Professor Matthew Fisher, Imperial College London, UK

Abstract

The Kingdom Fungi is a biodiverse and essential component of our habitable planet. However, the last 100 years have witnessed an increasing number of virulent emerging pathogenic fungi across ecosystems, with these infections causing the greatest disease-driven losses of biodiversity ever documented. Fungal life-history characteristics, namely high virulence, environmental persistence, broad host-ranges and flexible genomic architecture, predispose this kingdom to emergence as terminal pathogens across susceptible populations of hosts. Anthropogenic activity is a key factor that perturbs natural cycles of infection by increasing long-distance dispersal of inocula and through environmental forcing of infection dynamics. I demonstrate these concepts by analysing patterns and processes across the backdrop of globally-emerging amphibian-parasitising chytrid fungi. Genome sequencing defines ancient amphibian/chytrid associations that are being widely eroded as lineages of these fungi spread. Where divergent lineages of chytrids forge new contacts in nature, hybrids can form with potentially new epidemiologically-relevant traits, or outcompeted chytrids are themselves driven to extinction. Across newly infected regions where outbreaks are occurring, we see varied host population responses ranging from extirpation through to recovery that illustrate complex ecological-modifiers of the host/pathogen interaction. Long term field studies show that climate forces infection dynamics, with regional warming projected to heighten the severity of future outbreaks. These studies argue that ongoing 'fungal pollution' will increasingly cause the attrition of biodiversity unless steps are taken to tighten global biosecurity for this rapidly emerging class of pathogens.

09:30-10:00 Continental movement of fungi has resulted in unbalanced host relations and emerging diseases in forest ecosystems

Professor Jan Stenlid, Swedish University of Agricultural Sciences, Sweden

Abstract

Forest ecosystems are put under stress from adverse biotic and abiotic conditions. Over evolutionary time, host trees and pathogens are believed to enter a terror balance when occurring in proximity to each other. However, this balance is upset by introductions of potential pathogens from distant continents. The history of forest pathology is full of such introductions causing devastating outbreaks of disease. Predictions of unbalanced outcomes of host-pathogen interaction would be helped by classifying pathosystems based on the co-evolutionary history, but this is not always straightforward.  Genetic evidence such as signs of recent population expansions or genetic bottleneck effects, or patterns of ecological adaptation as well as tracing trade routes can help to elucidate disease history. Environmental factors can strongly influence tree disease. It is predicted that biotrophic, necrotrophic and vascular wilt pathogens, respectively, will create different patterns of host response to environmental stress. This is mediated by differential pathways of the various pathogens to interact with fundamental processes in the tree. Key components are the levels and distribution of non structural carbon hydrates allowing for above and below ground growth, reproduction, repair and defence. Environmental stresses, that are likely to increase in the light of climate change, can set novel limits to energy budgets for trees and climatic changes can open up new windows of opportunity for infection. Both these aspects can lead to emerging disease syndromes.  Also, multiple infections over time and space can act synergistically to create new challenges to forest ecosystems.

11:00-11:30 Linking ecology, impacts, and management in the emerging infectious disease of bats white-nose syndrome

Dr Kate Langwig, Harvard T.H. Chan School of Public Health, USA

Abstract

Emerging infectious diseases pose a key threat to wildlife populations. White-nose syndrome is an emerging fungal disease caused by the pathogen Pseudogymnoascus destructans. The disease has caused widespread declines in bat populations across eastern North America, and several species appear to be at risk of extinction. For white-nose syndrome, and other emerging fungal wildlife diseases, determining which species will persist and which will go extinct is critical for targeting disease management efforts. We find that mortality from white-nose syndrome appears to be driven primarily by infection intensity, with infection prevalence approaching 75% or greater across 6 bat species, and the highest loads in the most impacted species. We also find that some populations in regions where the disease has been present the longest have lower fungal loads, suggesting that some hosts may be developing mechanisms to persist with infection. In contrast, one species has been nearly extirpated from eastern North America, experiences uniformly high fungal loads, suggesting extinction may be imminent. These results provide key information needed to mitigate the causes and consequences of this devastating disease.

11:30-12:00 Snake fungal disease: Breaking the mould for emerging fungal diseases of wildlife

Dr Jeffrey Lorch, National Wildlife Health Center, USGS, USA

Abstract

In 2008, a disease affecting wild snake populations was reported from isolated locations in the Northeastern and Midwestern United States. The disease was characterised by grossly visible skin lesions and disfiguration of the head. Microscopically, fungal hyphae could be seen invading the skin, and the syndrome became known as snake fungal disease (SFD). In both geographic areas, infections were associated with the novel species of fungus, Ophidiomyces ophiodiicola, and follow-up laboratory studies demonstrated this fungus to be a primary pathogen and the cause of SFD. By 2015, SFD had been reported in most of the eastern half of the United States and was known to have a broad host range, affecting nearly all groups of snakes native to North America. Re-evaluation of retrospective cases of snakes with skin infections revealed that O. ophiodiicola had a nearly worldwide distribution in captive snakes prior to the disease being observed in wild snakes. This finding spurred concerns that O. ophiodiicola was an exotic pathogen introduced to North America through spillover from the pet trade. However, the spatial and temporal distribution of SFD cases does not indicate a pattern of spread suggestive of an introduced pathogen. Thus, unlike other emerging fungal diseases of wildlife such as white-nose syndrome of bats and chytridiomycosis of amphibians, mechanisms driving emergence of SFD remain unclear. Future work aimed at understanding the dynamics of SFD will be essential in protecting imperiled snake populations from this devastating disease.

13:30-14:00 A plague on plants - a mouldy future?

Professor Sarah Gurr, University of Exeter, UK

Abstract

Over the past centuries, crop diseases have led to the starvation of the people, the ruination of economies and the downfall of governments. Of the various challenges, the threat to plants of fungal infection outstrips that posed by bacterial and viral diseases combined. Indeed, fungal diseases have been increasing in severity and scale since the mid-20th Century and now pose a serious threat to global food security and ecosystem health.

We face a future blighted by known adversaries, by new variants of old foes and by new diseases. Modern agricultural intensification practices have heightened the challenge - the planting of vast swathes of genetically uniform crops, guarded by one or two inbred resistance genes, and use of single target site antifungals has hastened emergence of new virulent and fungicide-resistant strains. Climate change compounds the saga as we see altered disease demographics - pathogens are on the move poleward in a warming world.

This presentation will highlight some current notable and persistent fungal diseases. It will consider the evolutionary drivers underpinning emergence of new diseases and allude to the accelerators of spread. I will set these points in the context of recent disease modelling, which shows the global distributions of crop pathogens and their predicted movement and will discuss the concept of crop disease saturation.  I shall conclude with some thoughts on future threats and challenges, on fungal disease mitigation and of ways of enhancing global food security.

14:00-14:30 Keeping up with the plant destroyers - the 2-speed genomes of filamentous plant pathogens

Professor Sophien Kamoun, The Sainsbury Laboratory, UK

Abstract

Many species of fungi and oomycetes are plant pathogens of great economic importance. The genomes of these filamentous plant pathogens have revealed a remarkable diversity in genome size and architecture. Whereas the genomes of many parasites and bacterial symbionts have been reduced over time, the genomes of several lineages of filamentous plant pathogens have been shaped by repeat-driven expansions. In these lineages, the genes encoding proteins involved in host interactions are frequently polymorphic and reside within repeat-rich regions of the genome. This talk will review the properties of these adaptable genome regions and the mechanisms underlying their plasticity. I will also provide an update on our work on genome evolution in the lineage of the Irish potato famine organism Phytophthora infestans. Many plant pathogen species, including those in the P. infestans lineage, have evolved by host jumps followed by adaptation and specialization on distinct plant species. However, the extent to which host jumps and host specialization impact genome evolution remains largely unknown. The genomes of representative strains of four sister species of P. infestans revealed extremely uneven evolutionary rates across different parts of these pathogen genomes - a two-speed genome architecture. Genes in low density and repeat-rich regions show markedly higher rates of copy number variation, presence/absence polymorphisms, and positive selection. These loci are also highly enriched in genes induced in planta, such as disease effectors, implicating host adaptation in genome evolution. These results demonstrate that highly dynamic genome compartments enriched in non-coding sequences underpin rapid gene evolution following host jumps.

15:30-16:00 Clinical and environmental azole resistance of Aspergillus fumigatus

Dr Jacques Meis, Canisius Wilhelmina Hospital, The Netherlands

Abstract

Aspergillus fumigatus, a ubiquitously distributed opportunistic pathogen, is the global leading cause of aspergillosis. Azole antifungals play an important role in the management of aspergillosis. However in the last decade azole resistance in A. fumigatus isolates has been increasingly reported, especially in Europe, and this is potentially complicating effective disease management. The higher mortality rates observed in patients with invasive aspergillosis caused by azole resistant A. fumigatus isolates pose serious challenges to the mycologist for timely identification of resistance and appropriate therapeutic interventions. The ‘TR34/L98H’ mutation in the cyp51A gene of A. fumigatus is responsible for most multi-azole resistance seen in European countries, the Middle East, China, Australia and India. Azole-resistant isolates carrying this mutation have been reported from both patients and the environment. In addition, a newly emerging resistance mechanism, TR46/Y121F/T289A, conferring high voriconazole and variable itraconazole MICs was lately described in several European countries, Asia and the American continent. Environmental screening and routine antifungal susceptibility testing of clinically significant isolates should be considered in order to develop guidelines for local and national purposes. Considering that azole antifungal drugs are the mainstay of (oral) therapy, especially for chronic invasive and allergic aspergillosis, emergence of resistance will have profound impact on healthcare. This presentation highlights the global development of azole resistance in A. fumigatus and the possible relation with environmental fungicide use.

16:00-16:30 Ploidy dynamics and the rapid evolution of drug resistance

Professor Judith Berman, Tel Aviv University, Israel

Abstract

Candida albicans, the most prevalent human fungal pathogen, is generally diploid but other ploidy states clearly arise and are found not only in the laboratory but also in clinical isolates.  A major question motivating our work is how ploidy state and ploidy shifts affect pathogen evolution and survival, especially in responses to extreme stresses, such as exposure to antifungal drugs within the host. We are particularly interested in how rapidly different drug responses can be recruited to assist in stress survival. An important clue comes from the observation that 50% of isolates that are resistant to fluconazole (FLC), the most widely used antifungal, are aneuploid and that some specific aneuploidies can confer FLC resistance. Is aneuploidy the cause of resistance or does exposure to antifungals promote the appearance of aneuploidy? Our work indicates that the answer is yes: aneuploidy can be both a cause of drug resistance and a consequence of drug exposure. Furthermore, drug exposure elicits changes in cell cycle progression that lead to whole ploidy shifts. Survival in drug can be due to drug resistance, tolerance, persistence or heteroresistance. We are interested in the degree to which each of these strategies is used as well as the molecular mechanisms used to achieve these different strategies.

09:00-09:30 Medical mycology: recognising the true scale of a global problem

Professor Neil Gow, University of Aberdeen, UK

Abstract

Approximately one quarter of the world’s population are infected with fungi. More than 1.5 million people succumb to fungal infections each year – more than those dying from malaria and three times the number of breast cancer victims. Despite this high burden there are no antifungal vaccines or licensed immunotherapies and we urgently require more broad spectrum antifungal drugs and better point-of-care diagnostics. In all these respects fungal infections are challenging to deal with. Fungal immunopathology is usually organism-specific and requires a knowledge of the precise immunological setting and pathology of disease. In this regard human genomics, has defined important disease susceptibility mutations that have illuminated the mechanism of fungal immune recognition. Fungi rapidly adapt and change during the course of an infection and are therefore a moving target for our immune system. It is recognised that our immune responses are also shaped by the human myco-biome that is a stable part of the human microflora. Existing and new generations of antibiotics have increased the clinical armentarium, but antifungal drug resistance is becoming problematic in a number of settings and clinical interventions need to be guided by early diagnoses. This review and presentation will outline recent progress at the basic-clinical science interface that underpins how future clinical strategies may evolve to address the major health challenge imposed by fungal infections.

09:30-10:00 Emerging epidemics of plant disease: preparedness, monitoring and control

Professor Chris Gilligan, University of Cambridge, UK

Abstract

Drawing on current and recent work on emerging epidemics of plant disease in the UK, US, Africa and India, I propose to review briefly the sorts of questions that epidemiologists and agricultural planners are confronted with. Many of these questions centre on how long before the pest or disease arrives, how rapidly would it spread if it does arrive, when, where and how should we deploy surveillance, how effective is control likely to be, what is the risk of failure and how should control be deployed optimally? Another class of question concerns the risks associated with how we manage our agricultural and natural landscapes, for example, growing uniform stands of genetically homogeneous crops over large areas, over-use of pesticides and how to incentivise growers to manage disease effectively. Mathematical and computational modelling has an important role to play in integrating the current states of knowledge as a means to rationalise decision making under uncertainty. I shall illustrate ideas on risk and hazard maps to assess where disease is most likely to arrive and where it would have most impact, on allowing for uncertainty in order to assess the risks of failure as well as the probabilities of success in comparing disease control strategies and in how to deploy control effectively by coupling epidemiological with economic models.

11:00-11:30 Harnessing plant immune receptors for resistance to fungal pathogens

Dr Peter Dodds, CSIRO Agriculture, Australia

Abstract

Stem rust caused by Puccinia graminis tritici (Pgt) is one of the most serious diseases in wheat and the recent resurgence of this disease caused by new virulent races in Africa poses a threat to food security. The disease is combated mainly through breeding disease resistant varieties. Because the fungus evolves virulence towards previously resistant varieties, continuous breeding and identification of new sources of resistance is necessary to combat the threat of rust epidemics. Plant disease resistance can be triggered by specific recognition of microbial effectors by plant immune receptors that encode nucleotide binding leucine rich repeat (NB-LRR) receptors. Our work on the model system of flax (Linum usitatissium) resistance to the flax rust fungus (Melampsora lini) has provided insights into how the plant immune system recognises and responds to rust pathogens. We have been extending this work to wheat stem rust disease by targeted cloning of Resistance (R) genes in wheat and corresponding Avr genes in Pgt. We have recently isolated the Sr33 and Sr50 resistance genes from wheat and have begun functional analysis to determine how they trigger defence responses. We are also targeting effectors from Pgt that are recognised by wheat R genes. Understanding the nature of wheat R genes and the Avr proteins that they recognize will allow better prediction of R gene durability and choice of the optimal combinations of R genes to deploy in gene stacks.

11:30-12:00 Conservation in the face of emerging fungal threats

Professor Karen Lips, University of Maryland, USA

Abstract

Conservation solutions are rarely one-size-fits-all, and what works for one species may not work for another. Effective conservation measures are desperately needed but still sorely lacking in the case of amphibian chytridiomycosis. The tremendous host range of the pathogen Batrachochytrium dendrobatidis (Bd) and the presence of persistent environmental reservoirs are two features that have prevented development of effective conservation measures. Further, developing conservation measures to address Bd will be difficult when response to infection varies among species and populations, and depends on the composition of the amphibian community, host species traits, pathogen genotype, habitats, and climate conditions. Conservation is also hampered by a lack of data on the short-and long-term effects of Bd. Bd has been found on all continents (except Antarctica), but its history, and its effects on native amphibian populations are poorly known for most areas and for most species. In only a handful of cases do we have clear evidence that a community was recently invaded by an invasive lineage of chytrid, resulting in precipitous declines and dieoffs. Conservation efforts at these sites have focused on the removal of survivors and protection in captivity. In most regions, Bd is broadly distributed both geographically and taxonomically, often with little or no evidence of past epizootics, population declines, or pathogen invasion. What conservation measures should we employ at these sites, if any? Retrospective surveys of museum holdings have shown that the history of Bd at some sites has been many decades longer than expected, raising questions regarding the ability of scientists to detect the “Ghost of Chytrid Past” and the speed at which amphibians can adapt to disease. Should conservationists explore ways to facilitate amphibian evolution?  Twenty years of research has shown us that no silver bullet yet exists for protecting wild amphibians from chytridiomycosis; our most effective response may be imposing policies that restrict the movement of infected animals. We are testing this hypothesis in the US with a recent ban on salamander imports in an attempt to prevent the introduction of the newest chytrid, Bsal, into the US. This is a critical test because this new pathogen affects salamanders, and North America is a global hotspot for salamanders, with 10 families and 675 species, or ~65% of global species. Much could be lost, as salamanders and frogs are important members of many ecosystems, and also provide raw material for biomedical and biotech advances. Perhaps conservationists should be inspired by biodiversity to develop a portfolio of conservation measures to combat these and other wildlife diseases.

13:30-14:00 Fungal pathogenicity across host kingdoms

Professor Antonio di Pietro, University of Córdoba, Spain

Abstract

Fungal pathogens of plants and animals pose a severe threat to food security, biodiversity and public health. One of the most disruptive features of these agents is their dynamic host range. While some pathogens infect only a restricted number of species, others attack a wide range of organisms comprising both plants and animals. This dichotomy is epitomized by the Fusarium oxysporum species complex, which collectively infects over a hundred different crops provoking devastating economic losses in industrialized and developing countries. Clinical isolates of F. oxysporum have also been reported to cause life-threatening systemic infections in immunocompromised individuals. Remarkably, a single field isolate of F. oxysporum is able to kill tomato plants, immunodepressed mice and larvae of the insect host Galleria. While the genetic basis of cross-kingdom host range is unknown, sequencing of spontaneously originating fungal variants revealed a remarkable genomic plasticity, including large segmental duplications, translocations and deletions. Understanding the causes and phenotypic consequences of genome reshuffling may provide new insights into the mechanisms that drive virulence evolution and host adaptation in fungal cross-kingdom pathogens.

14:00-14:30 Fungal diseases and global food security

Professor Charles Godfray CBE FRS, University of Oxford, UK

Abstract

Repeated epidemics of fungal diseases have over the last few centuries have demonstrated the potential for these pathogens to cause extensive damage to crop yields and to severely affect the communities that depend on these food types.  We ask what the effects of a major fungal disease outbreak would be today in a world where the food system is substantially globalised.  We do this in two ways, first by looking at the consequences of a production shock caused by a pathogen affecting a major crop at a continental scale using an economic partial equilibrium model of the global food system.  Second by exploring different scenarios of responses to such a production shock that may involve mechanisms not captured by an economic model (for example political interventions involving trade disruption).  We compare the likely risk to global food security of fungal diseases with other current and forecast threats.

15:30-16:15 Universal access to fungal diagnostics and antifungal agents: a long way to go

Professor David Denning, University Hospital of South Manchester, UK

Abstract

Estimates of the global burden of serious fungal diseases place the main burden in 3 categories: potentially life-threatening infections in AIDS (cryptococcal meningitis, Pneumocystis pneumonia and disseminated histoplasmosis); life-threatening infection in hospitalised and immunocompromised patients (invasive candidiasis and aspergillosis); and chronic debilitating lung infections and allergies (‘fungal asthma’ and chronic pulmonary aspergillosis, many after TB). Deaths from fungal infection in AIDS are estimated to exceed 700,000, nearly 50% of the total AIDS deaths.

Recently major improvements in diagnostics allow earlier diagnosis and better therapy, even discontinuing unnecessary antibacterial and antifungal therapies. There is a major need to build capacity and expertise in this area, to reduce deaths, reduce pressure on antibacterial and antifungal resistance and to reduce ill-health. Adequate and well established antifungal agents have been available since the 1960’s (amphotericin B), 1970’s (flucytosine) and 1990’s (fluconazole and itraconazole), yet the first 2 are unavailable in many countries.

The potential impact of improved access to fungal diagnostic tests and antifungal therapy will be illustrated by reference to reducing deaths in AIDS. Most patients who die of AIDS are in their 30’s. If at least 60% of the 35 million HIV population has access to fungal diagnosis and therapy by 2020, conservative estimates of reduced deaths from cryptococcal disease, Pneumocystis pneumonia, disseminated histoplasmosis and chronic pulmonary aspergillosis are a fall between from 233,750 to 163,000, from 260,000 to 97,500, from 80,000 to 32,000 and from 56,000 to 22,500 respectively, a cumulative total of 1,642,000 people, who do not die in the prime of life.

16:15-17:00 Overview and future directions

Professor John W. Taylor, University of California, Berkeley, USA