A plague on plants - a mouldy future?
Professor Sarah Gurr, University of Exeter, UK
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.
Keeping up with the plant destroyers - the 2-speed genomes of filamentous plant pathogens
Professor Sophien Kamoun, The Sainsbury Laboratory, UK
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.
Clinical and environmental azole resistance of Aspergillus fumigatus
Dr Jacques Meis, Canisius Wilhelmina Hospital, The Netherlands
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.
Ploidy dynamics and the rapid evolution of drug resistance
Professor Judith Berman, Tel Aviv University, Israel
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.