Infection and transmission heterogeneity of a multi-host pathogen (Batrachochytrium dendrobatidis) within an amphibian community

The majority of parasites infect multiple hosts. As the outcome of the infection is different in each of them, most studies of wildlife disease focus on the few species that suffer the most severe consequences. However, the role that each host plays in the persistence and transmission of infection can be crucial to understanding the spread of a parasite and the risk it poses to the community. Current theory predicts that certain host species can modulate the infection in other species by amplifying or diluting both infection prevalence and infection intensity, both of which have implications for disease risk within those communities. The fungus Batrachochytrium dendrobatidis (Bd), the causal agent of the disease chytridiomycosis, has caused global amphibian population declines and extinctions. However, not all infected species are affected equally, and thus Bd is a good example of a multi-host pathogen that must ultimately be studied with a community approach. To test whether the common midwife toad Alytes obstetricans is a reservoir and possible amplifier of infection of other species, we used experimental approaches in captive and wild populations to determine the effect of common midwife toad larvae on infection of other amphibian species found in the Peñalara Massif, Spain. We observed that the most widely and heavily infected species, the common midwife toad, may be amplifying the infection loads in other species, all of which have different degrees of susceptibility to Bd infection. Our results have important implications for performing mitigation actions focused on potential ‘amplifier’ hosts and for better understanding the mechanisms of Bd transmission.Peer reviewe

Long-Term Monitoring of Amphibian Populations of a National Park in Northern Spain Reveals Negative Persisting Effects of Ranavirus, but Not Batrachochytrium dendrobatidis

Amphibians are the most highly threatened vertebrates, and emerging pathogens are a serious threat to their conservation. Amphibian chytrid fungi and the viruses of the Ranavirus genus are causing disease outbreaks worldwide, including in protected areas such as National Parks. However, we lack information about their effect over amphibian populations in the long-term, and sometimes these mortality episodes are considered as transient events without serious consequences over longer time-spans. Here, we relate the occurrence of both pathogens with the population trends of 24 amphibian populations at 15 sites across a national Park in northern Spain over a 14-year period. Just one out 24 populations presents a positive population trend being free of both pathogens, while seven populations exposed to one or two pathogens experienced strong declines during the study period. The rest of the study populations (16) remain stable, and these tend to be of species that are not susceptible to the pathogen present or are free of pathogens. Our study is consistent with infectious diseases playing an important role in dictating amphibian population trends and emphasizes the need to adopt measures to control these pathogens in nature. We highlight that sites housing species carrying Ranavirus seems to have experienced more severe population-level effects compared to those with the amphibian chytrid fungus, and that ranaviruses could be just as, or more important, other more high-profile amphibian emerging pathogens

Climate warming triggers the emergence of native viruses in Iberian amphibians

The number of epizootics in amphibian populations caused by viruses of the genus Ranavirus is increasing worldwide. Yet, causes for pathogen emergence are poorly understood. Here, we confirmed that the Common midwife toad virus (CMTV) and Frog virus 3 (FV3) are responsible for mass mortalities in Iberia since the late 1980s. Our results illustrate the Iberian Peninsula as a diversity hotspot for the highly virulent CMTV. Although this pattern of diversity in Europe is consistent with spread by natural dispersal, the exact origin of the emergence of CMTV remains uncertain. Nevertheless, our data allow hypothesizing that the Iberian Peninsula might harbor the ancestral population of CMTVs that could have spread into the rest of Europe. In addition, we found that climate warming could be triggering the CMTV outbreaks, supporting its endemic status in the Iberian Peninsula.info:eu-repo/semantics/acceptedVersio

Prioritization of Therapeutic Targets and Trial Design in Cirrhotic Portal Hypertension.

Portal hypertension is the main driver of cirrhosis decompensation, the main determinant of death in patients with cirrhosis. Portal hypertension results initially from increased intrahepatic vascular resistance. Later, increased inflow from splanchnic vasodilation and increased cardiac output lead to a further increase in portal pressure. Reducing portal pressure in cirrhosis results in better outcomes. Removing the cause of cirrhosis might improve portal pressure. However, this is a slow process and patients may continue to be at risk of decompensation. Additionally, for some chronic liver diseases, such as non-alcoholic fatty liver disease, etiological treatments are not yet available. Therefore, there is a need to develop better therapies specifically aimed at reducing portal pressure. For over 35 years, the mainstay of such therapy has been the use of nonselective beta-blockers that act by reducing portal venous inflow. Recently, many drugs (mainly targeting intrahepatic mechanisms) have shown promise in pre-clinical and early clinical studies and may act alone or synergistically with nonselective beta-blockers in reducing portal pressure in cirrhosis. The objective of this position paper is to propose a novel framework for the design of clinical trials (phase 1, 2 and 3) in patients with cirrhosis and portal hypertension and to prioritize novel targets and pharmacological therapies in this setting. We have focused the discussion on patients with compensated cirrhosis. The paper summarizes discussions held at The American Association for the Study of Liver Diseases (AASLD) Industry Colloquium in January 2018, with the participation of clinical and translational investigators, regulatory professionals and industry partners

Multiple emergences of genetically diverse amphibian-infecting chytrids include a globalized hypervirulent recombinant lineage

Batrachochytriumdendrobatidis (Bd) is a globally ubiquitous fungal infection that has emerged to become a primary driver of amphibian biodiversity loss. Despite widespread effort to understand the emergence of this panzootic, the origins of the infection, its patterns of global spread, and principle mode of evolution remain largely unknown. Using comparative population genomics, we discovered three deeply diverged lineages of Bd associated with amphibians. Two of these lineages were found in multiple continents and are associated with known introductions by the amphibian trade.We found that isolates belonging to one clade, the global panzootic lineage (BdGPL) have emerged across at least five continents during the 20th century and are associated with the onset of epizootics in North America, Central America, the Caribbean, Australia, and Europe. The two newly identified divergent lineages, Cape lineage (BdCAPE) and Swiss lineage (BdCH), were found to differ in morphological traits when compared against one another and BdGPL, and we show that BdGPL is hypervirulent. BdGPL uniquely bears the hallmarks of genomic recombination, manifested as extensive intergenomic phylogenetic conflict and patchily distributed heterozygosity. Wepostulate that contact between previously genetically isolated allopatric populations of Bd may have allowed recombination to occur, resulting in the generation, spread, and invasion of the hypervirulent BdGPL leading to contemporary disease-driven losses in amphibian biodiversity.Peer Reviewe

Microbiome function predicts amphibian chytridiomycosis disease dynamics

[Background] The fungal pathogenBatrachochytrium dendrobatidis (Bd) threatens amphibian biodiversity and ecosystem stability worldwide. Amphibian skin microbial community structure has been linked to the 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 is inconsistent with microbial functional redundancy, indicating that differences in microbial taxonomy drive functional variation. Shotgun metagenomic analyses support these findings, with similar disease-associated patterns in beta diversity. Analysis of differentially abundant bacterial genes and pathways indicated that bacterial environmental sensing and Bd resource competition are likely to be important in driving infection outcomes. [Conclusions] Bd infection drives altered microbiome taxonomic and functional profiles across laboratory and field environments. Our application of multi-omics analyses in experimental and field settings robustly predicts Bd disease dynamics and identifies novel candidate biomarkers of infection. [MediaObject not available: see fulltext.]K.A.B. was funded by a CASE studentship from NERC, NERC Biomolecular Analysis Facility grant (NBAF939) and an E.P. Abraham Junior Research Fellowship from St Hilda’s College, University of Oxford. M.C.F and T.W.J.G. were funded by NERC award NE/E006701/1 and the Biodiversa project RACE: Risk Assessment of Chytridiomycosis to European Amphibian Biodiversity. T.W.J.G was also funded by Research England and NERC NE/S000062/1. D.S.S. and A.L. received funding through the project People, Pollution, and Pathogens financed through the call “Mountains as Sentinels of Change” by the Belmont-Forum (ANR-15-MASC-0001 - P3, DFG-SCHM3059/6-1, NERC-1633948, NSFC-41661144004). D.S.S. holds the AXA Chair for Functional Mountain Ecology funded by the AXA Research Fund through the project GloMEc and M.C.F. is a fellow in the CIFAR ‘Fungal Kingdoms’ Program

Successful elimination of a lethal wildlife infectious disease in nature

Methods to mitigate the impacts of emerging infectious diseases affecting wildlife are urgently needed to combat loss of biodiversity. However, the successful mitigation of wildlife pathogens in situ has rarely occurred. Indeed, most strategies for combating wildlife diseases remain theoretical, despite the wealth of information available for combating infections in livestock and crops. Here, we report the outcome of a 5-year effort to eliminate infection with Batrachochytrium dendrobatidis affecting an island system with a single amphibian host. Our initial efforts to eliminate infection in the larval reservoir using a direct application of an antifungal were successful ex situ but infection returned to previous levels when tadpoles with cleared infections were returned to their natal sites. We subsequently combined antifungal treatment of tadpoles with environmental chemical disinfection. Infection at four of the five pools where infection had previously been recorded was eradicated, and remained so for 2 years post-application.This work was funded by Fundacio´n General CSIC, Banco Santander and BiodivERsA project RACE.Peer reviewe

Soybean Date of Planting and Maturity in Northern Iowa

Inevitably, every year soybean planting gets delayed or needs to be replanted because of weather somewhere in Iowa. Even if soybean planting starts and progresses in a timely manner, there always is the question of what maturity group should be planted. This trial was setup to determine what maturities are well suited for a given geographic location, but also how maturity selection should be adjusted as planting dates get pushed into late spring