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Berger, L.

Publications and source records attributed to Berger, L..

7 recordsLinked to original sources

Glutathione impacts both Batrachochytrium dendrobatidis virulence and amphibian cellular defence in a chytridiomycosis model

Glutathione has important roles in diverse infections, yet its involvement in the interaction between the deadly fungal pathogen Batrachochytrium dendrobatidis (Bd) and its amphibian hosts is still unclear. Using in vitro assays and a cell infection model, we examined how glutathione influences Bd virulence traits and cellular host disease resistance. For Bd, inhibition of glutathione reductase rapidly killed zoospores, indicating that glutathione is essential for this pathogen. In addition, exposure to exogenous glutathione promoted the potential for virulence through accelerated and increased zoospore release. In host amphibian cells, Bd infection decreased intracellular glutathione content and increased reactive oxygen species, suggesting that chytridiomycosis pathogenesis may involve oxidative stress. Depletion of host glutathione before exposure to Bd increased infection severity and Bd growth, whereas amphibian cells with slightly elevated glutathione levels were partially protected against Bd. However, manipulation of host glutathione levels after the establishment of Bd infection did not impact its intracellular growth, implying that the host glutathione-mediated resistance only occurs during the initial Bd invasion process. Importantly, this effect of glutathione on host resistance is not a general response to pathogens, as it was not observed in cells exposed to viral pathogen FV3. As glutathione increased both infectious zoospore production and host resistance to zoospore infection, our study suggests that this antioxidant may play an important role in the host/pathogen interaction during chytridiomycosis. Thus, environmental conditions and therapeutic approaches that affect glutathione systems in the host and/or pathogen have the potential to alter chytridiomycosis dynamics and should be further explored.

pathology↗

Developmental vitamin A deficiency induces sex-specific reward processing alterations through a dysregulation of the mesolimbic dopamine transmission in mice

Neurodevelopmental psychiatric diseases such as schizophrenia or affective disorders share common symptomatic dimensions, in particular reward processing dysfunctions, associated with dysregulation of dopamine (DA) transmission. Retinoic acid (RA) homeostasis is altered across psychiatric disorders but whether impaired developmental RA signaling impacts the functionality of DA-related reward processing at adulthood remains poorly explored. Herein, we explored in male and female mice how developmental vitamin A deficiency (VAD), as a model of blunted RA signaling, could impact motivational processes through a modulation of mesolimbic DA transmission. Behavioral performances were evaluated using operant conditioning tasks, parallel with investigations of the integrity of DA transmission through biochemical analyses of markers of DA transmission and measures of DA dynamics using DA biosensor coupled with fiber photometry. Finally, chemogenetic manipulation of the mesolimbic DA pathway was used to normalize DA transmission and assess the effect on motivational performance in VAD offspring. Developmental VAD induced sex-specific alterations of reward-related processes at adulthood. Indeed, while female behavioral performances were spared, VAD males exhibited elevated instrumental performance and impulsivity. These behavioral alterations were coherent with reduced DA transporter (DAT) expression and increased DA dynamic in the mesolimbic pathway. Strikingly, chemogenetic inhibition of the mesolimbic DA pathway normalized motivational performance in VAD males. Our results show that developmental RA hyposignaling induces sex-specific reward processing alterations in adulthood through hyperactivity of the mesolimbic DA pathway. Our data support that developmental impairment in RA signaling might be at the core of reward-related symptoms across psychiatric disorders.

neuroscience↗

Latitudinal gradients in stable hydrogen isotopes of North American trees

Stable hydrogen isotopes ({delta}2H values) of plant matter provide information about ambient climate conditions and physiological processes.{delta} 2H values of tree stem wood methoxy groups ({delta}2HTM) are increasingly used to reconstruct the isotope composition of precipitation ({delta}2Hprecip) and temperature variability in mid latitudes regions. However, empirical evidence of the basic latitudinal gradients in North America and their inter-continental context are still missing. We sampled 104 tree cores in 13 North American sites ranging from 38{degrees}-69{degrees}N and investigated the relationship between{delta} 2HTM and{delta} 2Hprecip values. Recorded{delta} 2HTM values are highly depleted in 2H relative to meteoric water and align closely with predictions from a biochemical model. Reconstructed temperature changes, derived from{delta} 2HTM values, agree well with instrumental data in North American since 1932. Our results reveal that the latitudinal gradients of{delta} 2HTM values closely resemble{delta} 2Hprecip values across North America. When combining these spatial patterns with{delta} 2HTM and{delta} 2Hprecip data from Europe a strong correlation (R2 = 0.94, p < 0.001) and a consistent fractionation of -193 {+/-} 13 mUr, representative for Northern Hemisphere mid-to-high latitude sites, is established. The validation across North American and European transects serves as a foundational basis for advancing applications in biogeochemistry and paleoclimate research.

plant biology↗

Exposure to low doses of Batrachochytrium dendrobatidis reveals variation in resistance in the Critically Endangered southern corroboree frog

Chytridiomycosis poses a significant extinction threat to many amphibians, including the critically endangered southern corroboree frog (Pseudophryne corroboree). Captive breeding programs have become essential to maintain populations while effective long-term conservation strategies are developed. Understanding the variation in susceptibility to chytridiomycosis within this species is essential in exploring the potential for selective breeding to enhance disease resistance. In this study, we conducted a large-scale Batrachochytrium dendrobatidis (Bd) exposure experiment involving 972 juvenile P. corroboree selected to ensure a broad genetic representation of the species. Three replicate experiments were conducted under uniform conditions, to assess individual susceptibility and compare results across replicate experiments. Significant variation was observed within and between experiments, with individual survival rates ranging from 44-74% across experiments, influenced notably by the zoo in which frogs were bred. Remarkably, 21-47% of exposed frogs remained Bd-negative, suggesting potential innate resistance. Infection intensity correlated positively with body condition, in one experiment, while age and size showed inconsistent effects on survival and infection rates across experiments, but younger and smaller frogs were more susceptible to infection and had lower survival. Among frogs that became infected, none cleared infection, with most progressing to terminal stages within an average of 69 days (ranging from 33 to 97 days). However, a few individuals maintained stable infection loads without displaying clinical signs of chytridiomycosis. This observed phenotypic variation in P. corroboree responses to Bd highlights the potential for selective breeding to improve survival outcomes in this species. The dataset generated from this study will be instrumental in guiding breeding strategies that strengthen conservation efforts for this critically endangered species.

zoology↗

Tracking of antibiotic resistance transfer and rapid plasmid evolution in a hospital setting by Nanopore sequencing

BackgroundInfection of patients with multidrug-resistant (MDR) bacteria often leave very limited or no treatment options. The transfer of antimicrobial resistance genes (ARG) carrying plasmids between bacterial species by horizontal gene transfer represents an important mode of expansion of ARGs. Here, we evaluated the application of Nanopore sequencing technology in a hospital setting for monitoring the transfer and rapid evolution of antibiotic resistance plasmids within and across multiple species.\n\nResultsIn 2009 we experienced an outbreak with an extensively multidrug resistant P. aeruginosa harboring the carbapenemase enzyme blaIMP-8, and in 2012 the first Citrobacter freundii and Citrobacter werkmanii harboring the same enzyme were detected. Using Nanopore and Illumina sequencing we conducted a comparative analysis of all blaIMP-8 bacteria isolated in our hospital over a 6-year period (n = 54). We developed the computational platforms pathoLogic and plasmIDent for Nanopore-based characterization of clinical isolates and monitoring of ARG transfer, comprising de-novo assembly of genomes and plasmids, polishing, QC, plasmid circularization, ARG annotation, comparative genome analysis of multiple isolates and visualization of results. Using plasmIDent we identified a 40 kb plasmid carrying blaIMP-8 in P. aeruginosa and C. freundii, verifying that plasmid transfer had occurred. Within C. freundii the plasmid underwent further evolution and plasmid fusion, resulting in a 164 kb mega-plasmid, which was transferred to C. werkmanii. Moreover, multiple rearrangements of the multidrug resistance gene cassette were detected in P. aeruginosa, including deletions and translocations of complete ARGs.\n\nConclusionPlasmid transfer, plasmid fusion and rearrangement of the multidrug resistance gene cassette mediated the rapid evolution of opportunistic pathogens in our hospital. We demonstrated the feasibility of tracking plasmid evolution dynamics and ARG transfer in clinical settings in a timely manner. The approach will allow for successful countermeasures to contain not only clonal, but also plasmid mediated outbreaks.

genomics↗

Genetic potential for disease resistance in a critically endangered frog decimated by chytridiomycosis.

Southern corroboree frogs (Pseudophryne corroboree) have been driven to functional extinction in the wild after the emergence of the amphibian fungal pathogen Batrachochytrium dendrobatidis (Bd) in southeastern Australia in the 1980s. This species is currently maintained in a captive assurance colony and is managed to preserve the genetic diversity of the founding populations. However, it is unlikely that self-sustaining wild populations can be re-established unless Bd resistance increases. We performed a Bd-challenge study to investigate the association between genetic variants of the major histocompatibility complex class IA (MHC) and genome-wide single nucleotide polymorphisms (SNPs). We also investigated differences in Bd susceptibility among individuals and populations, and the genetic diversity and population genetic structure of four natural P. corroboree populations. We found several MHC alleles and SNPs associated with Bd infection load and survival, provide evidence of significant structure among populations, and identified population-level differences in the frequency of influential variants. We also detected evidence of positive selection acting on the MHC and a subset of SNPs as well as evidence of high genetic diversity in P. corroboree populations. We suggest that low interbreeding rates may have contributed to the demise of this species by limiting the spread of Bd resistance genes. However, our findings demonstrate that despite dramatic declines there is potential to restore high levels of genetic diversity in P. corroboree. Additionally, we show that there are immunogenetic differences among captive southern corroboree frogs, which could be manipulated to increase disease resistance and mitigate the key threatening process, chytridiomycosis.

genomics↗

Development and worldwide use of a non-lethal and minimal population-level impact protocols for the isolation of chytrids from amphibians

Parasitic chytrid fungi have emerged as a significant threat to amphibian species worldwide, necessitating the development of techniques to isolate these pathogens into sterile culture for research purposes. However, early methods of isolating chytrids from their hosts relied on killing amphibians. We modified a pre-existing protocol for isolating chytrids from infected animals to use toe clips and biopsies from toe webbing rather than euthanizing hosts, and distributed the protocol to interested researchers worldwide as part of the BiodivERsA project RACE - here called the RML protocol. In tandem, we developed a lethal procedure for isolating chytrids from tadpole mouthparts. Reviewing a database of use a decade after their inception, we find that these methods have been widely applied across at least 5 continents, 23 countries and in 62 amphibian species, and have been successfully used to isolate chytrids in remote field locations. Isolation of chytrids by the non-lethal RML protocol occured in 18% of attempts with 207 fungal isolates and three species of chytrid being recovered. Isolation of chytrids from tadpoles occured in 43% of attempts with 334 fungal isolates of one species (Batrachochytrium dendrobatidis) being recovered. Together, these methods have resulted in a significant reduction and refinement of our use of threatened amphibian species and have improved our ability to work with this important group of emerging fungal pathogens.

ecology↗