Understanding links between microbial communities and emerging fungal pathogens in complex ecosystem

Lead Research Organisation: Zoological Society of London
Department Name: Insitute of Zoology

Abstract

Modern-day amphibians are known to be suffering rates of extinction that far exceed any other class of vertebrates, including those experienced by mammals and birds, and nearly one third of amphibian species are threatened. The question of why amphibians are going extinct at these accelerated rates has puzzled scientists for three decades. A clue to the mystery came about when scientists working in Central America and Australia noted that the rapid declines in amphibian biodiversity were spreading in a wave-like manner. These patterns of decline were caused by an emerging infectious disease and in 1997 researchers discovered that a fungal pathogen, called a 'chytrid', was the cause, naming it Batrachochytrium dendrobatidis (Bd). Since then, our research has identified South East Asia as the cradle of this amphibian pandemic, and has mapped the spread of Bd worldwide At the same time, alongside finding regions of the world where Bd is highly pathogenic, we have also discovered places where it is not causing any obvious disease which begs the question Why?

Increasingly, we find that the invasion, establishment and amplification of Bd in uninfected amphibians is strongly influence by the microbial communities that are found inhabiting the skins of amphibians. As Alexander Fleming famously discovered, microbes predate and attack one another with a diverse array of strategies and our research seeks to understand how this microbial warfare influences whether an amphibian community survives, or succumbs, to its infection. This question will be addressed by using high-throughput DNA sequencing technologies to characterise the microbes on amphibians around the world using molecular barcoding techniques. Our main idea is that the amphibians that survive infection infection are 'clothed' by a protective community of bacteria and fungi. We will show whether this it true, then will attempt to identify the toxic molecules that are protecting the amphibians from their chytrid onslaught.

Finally, we will seek to isolate and grow microbes that are protective against Bd - sometimes called 'probiotics'. Here, we will extend our focus to include fungi because (and as Fleming showed) they can be very potent protectors against invasive organisms. We already have isolated candidate fungal 'promycotics', and we will use experiments to determine whether they do in fact protect amphibians against lethal infection by Bd; such promycotics may then offer a much-needed biocontrol against emerging pathogens such as Bd. This, ultimately, is the major applied goal of our project.

Planned Impact

Who will benefit from our research?

Our work will be of direct use to those working to stem the spread of invasive species and infection. Major project stakeholders are the GB non-native species secretariat, DEFRA, the Animal and Plant Health Agency and Natural England whom all work to contain the spread of infection into GB. Alongside Government, there is a UK-wide network of NGO's whom work on amphibian conservation and the threat that chytrids present - two of our Project Partners are FrogLife whom have supported our work on Great Crested Newts over the years. Outside of the UK, there is a global network of conservation biologists, international NGOs ('Save the Frogs!'; 'Amphibian Ark'; the IUCN), national NGOs ('KARCH'; 'Museo Nacional Ciencias Naturales') whom we are actively engaged in with in facilitating attempts to understand and mitigate the panzootic of chytrids and other fungal infections (bat White Nose Syndrome, sudden oak death, crayfish plague, Ash dieback). Our methods and data are of direct relevance to understanding patterns of transmission and host loss. As such our research will directly impact the policy and activities that these end-users and stakeholders deliver: A direct example is our 2014 work with the Morris Animal Foundation and Mohamed Bin Zayed Species Conservation Fund to assess whether an outbreak of Bd is occurring on Madagascar - this resulted in a 'top 100 paper' out of 11,000 in Scientific Reports 2015.

More widely, our research addresses the broader issue of biosecurity and pathogen evolution. A major output of globalisation is a more homogenised biota and it is becoming increasingly recognised that novel plagues constitute a major threat to biodiversity and ecosystem function. Our work is of interest to policy advisors and trade bodies (the OIE, the EU, OECD) and scientists working to understand the ecosystem-level impact of invasive species. Our main point of interaction with the UK government is via the 'Amphibians Health Committee' that comprises academics, NGO's and government officials (APHA/ VLA/ DEFRA/ NNSS): this committee works to ensure that the UK response to the introduction of new pathogenic chytrids is evidence-based and not reactive.

2. How will they benefit?

Project outputs framed for the visiting public at Imperial College and ZSL: Visitors to ZSL's London Zoo (annually 1 million) can see our research outputs via the newly refurbished AmphibianConservation Centre. Two dedicated video screens report results of the amphibian disease research program and daily live presentations made by keepers, researchers and trained presenters provide a proactive platform for informing the public regarding amphibian diseases, amphibian conservation, and our efforts to understand and mitigate the problem. Additionally, several thousand Greater London school children take part in ZSL's EdExcel program, a large component of which comprises presentations by members of the amphibian disease research team. Regular public symposia have amphibian disease issues as the topic, hosted by notables such as Sir David Attenborough. At Imperial College the team regularly presents at our summer Science Festival and Fringe event - these event's attract many thousands of public participants.

Publications

10 25 50
 
Description Microbial communities were shown to have a functional contribution to the strength of disease epidemics. They are targets for further research into controlling wildlife diseases
Exploitation Route Already we have partnered again with Imperial College in the Leverhulme Centre for the Holobiont. We are using amphibians as a model system for understanding the relationships between macro- and microbiological diversity and how this relates to overall ecosystem function
Sectors Environment

 
Title Challenging a host-pathogen paradigm: Susceptibility to chytridiomycosis is decoupled from genetic erosion 
Description The putatively positive association between host genetic diversity and the ability to defend against pathogens has long attracted the attention of evolutionary biologists. Chytridiomycosis, a disease caused by the chytrid fungus Batrachochytrium dendrobatidis (Bd), has emerged in recent decades as a cause of dramatic declines and extinctions across the amphibian clade. Bd susceptibility can vary widely across populations of the same species, but the relationship between standing genetic diversity and susceptibility has remained notably underexplored so far. Here, we focus on a putatively Bd-naive system of two mainland and two island populations of the common toad (Bufo bufo) at the edge of the species' range, and use controlled infection experiments and dd-RAD sequencing of >10,000 SNPs across 95 individuals to characterise the role of host population identity, genetic variation and individual body mass in mediating host response to the pathogen. We found strong genetic differentiation between populations and marked variation in their susceptibility to Bd. This variation was not, however, governed by isolation-mediated genetic erosion, and individual heterozygosity was even found to be negatively correlated with survival. Individual survival during infection experiments was strongly positively related to body mass, which itself was unrelated to population of origin or heterozygosity. Our findings underscore the general importance of context-dependency when assessing the role of host genetic variation for the ability of defence against pathogens. 
Type Of Material Database/Collection of data 
Year Produced 2022 
Provided To Others? Yes  
URL http://datadryad.org/stash/dataset/doi:10.5061/dryad.9s4mw6mjb
 
Description Cross-continental, interlineage competition and virulence of Batrachochytrium dendrobatidis 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Presentation at 9th World Congress of Herpetology, session Batrachochytrium dendrobatidis 1. Established new contacts with teams also investigating chytrid competition dynamics
Year(s) Of Engagement Activity 2020
URL http://www.wchnz.com/wch2020
 
Description Did Bd-CAPE drive the Kihansi spray toad (Nectophrynoides asperginis) to extinction in the wild? 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact PDRA presentation on chytrid genome associated with first and only reported decline of amphibians on the African continent. Numerous African researchers engaged afterwards to discuss options for surveys and post-decline investigations of amphibians.
Year(s) Of Engagement Activity 2020
URL http://www.wchnz.com/wch2020
 
Description Mitigating single pathogen and co-infections that threaten amphibian biodiversity 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact First major scientific event examining how to mitigate single and multiple pathogens in amphibian populations threatened by infectious diseases. Conveners include PIs from 3 NERC standard grants. 2 day symposium involving researchers from across Europe, the Americas and Australasia, and 2 single day workshops, 1 on microbiomes and 1 doing a mock disease intervention. One publication from 2nd workshop. Attendees report overwhelmingly as to quality and reach of event, new collaborations formed and suggestion this become a once every few years event.
Year(s) Of Engagement Activity 2019
 
Description Resolving Batrachochytrium dendrobatidis lineage distribution and ecology in South Africa 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact PhD student presentation on developing and applying lineage specific qPCRs to understand lineage interactions in nature. Extensive interest in developing similar tools for other lineages and applying existing tools to European settings.
Year(s) Of Engagement Activity 2020
URL http://www.wchnz.com/wch2020