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All sourcesNASA NTRSDOE OSTI
NASA NTRS2025

Influence of Microgravity on Bacterial Pathogen Virulence and Immune Cell Function—Relevance for Infectious Disease Risk During Spaceflight

Spaceflight has measurable impacts on astronaut immune profiles as well as the virulence patterns of bacterial pathogens. Data with respect to human immunity indicate diminished T and NK cell function, altered cytokine profiles, persistent inflammation, and latent herpesvirus reactivation. Furthermore, evaluation of International Space Station (ISS) crewmembers gives evidence of compromised immunity, including atypical allergy, infectious disease, and dermatitis. Data with respect to certain human bacterial pathogens suggest modified virulence that may be enhanced. It is therefore critical to examine this interaction of immune dysregulation and increased microbial virulence and whether it might synergistically increase the risk of infectious disease to crew members. The goal of this study is to use modeled microgravity to study the impact of medically significant ISS bacteria that may have altered virulence on the immune response of the host. This study consists of two primary aims to assess this relationship. First, immune cells will be collected from healthy test subjects and cultured in static or in modeled microgravity conditions together with either control pathogens or with microgravity conditioned pathogens that were grown in bioreactors. Second, immune cells will be collected from astronauts before, during, and after flight and co-cultured with the control or the microgravity conditioned bacteria. Three pathogens were selected for this investigation: Pseudomonas aeruginosa , Salmonella enterica serovar Enteritidis and Burkholderia cepacia . Previously, the optimal cell to bacteria ratios that produce the greatest immune cell responses have been derived for these three bacteria. Cellular activation, as determined by the induction of cell surface activation markers and cytokine profiles, will be measured. Interactions between cells and bacteria will be assessed using fluorescent and electron microscopy techniques. This study will provide critical information to help understand how microgravity alters microbial virulence and the associated infectious disease risk to crewmembers during spaceflight missions. Over the past year, the Immunology and Microbiology laboratories at NASA Johnson Space Center have collaborated to process the astronaut subject samples to complete the last year of the flight portion of this study. This included the completion of four astronaut subjects full mission sampling sets. Sample processing included innate and adaptive cell flow cytometry as well as analysis of cytokine concentrations in the supernatant. The ground control segment of the study will take place during FY25 which involves parallel infections run under static and clinostat conditions. The acquired data sets over this 3-year study are now being analyzed to provide a comprehensive set of results and conclusions that will contribute to a more effective risk assessment for astronauts during spaceflight regarding this host-pathogen context.

Immunology↗
DOE OSTI2018

Modeling Host-Pathogen Interactions in the Context of the Microenvironment: Three-Dimensional Cell Culture Comes of Age

Tissues and organs provide the structural and biochemical landscapes upon which microbial pathogens and commensals function to regulate health and disease. While flat two-dimensional (2-D) monolayers composed of a single cell type have provided important insight into understanding host-pathogen interactions and infectious disease mechanisms, these reductionist models lack many essential features present in the native host microenvironment that are known to regulate infection, including three-dimensional (3-D) architecture, multicellular complexity, commensal microbiota, gas exchange and nutrient gradients, and physiologically relevant biomechanical forces (e.g., fluid shear, stretch, compression). Here, a major challenge in tissue engineering for infectious disease research is recreating this dynamic 3-D microenvironment (biological, chemical, and physical/mechanical) to more accurately model the initiation and progression of host-pathogen interactions in the laboratory. Here we review selected 3-D models of human intestinal mucosa, which represent a major portal of entry for infectious pathogens and an important niche for commensal microbiota. We highlight seminal studies that have used these models to interrogate host-pathogen interactions and infectious disease mechanisms, and we present this literature in the appropriate historical context. Models discussed include 3-D organotypic cultures engineered in the rotating wall vessel (RWV) bioreactor, extracellular matrix (ECM)-embedded/organoid models, and organ-on-a-chip (OAC) models. Collectively, these technologies provide a more physiologically relevant and predictive framework for investigating infectious disease mechanisms and antimicrobial therapies at the intersection of the host, microbe, and their local microenvironments.

3-D↗
DOE OSTI2019

Cell-length heterogeneity: a population-level solution to growth/virulence trade-offs in the plant pathogen Dickeya dadantii

Necrotrophic plant pathogens acquire nutrients from dead plant cells, which requires the disintegration of the plant cell wall and tissue structures by the pathogen. Infected plants lose tissue integrity and functional immunity as a result, exposing the nutrient rich, decayed tissues to the environment. One challenge for the necrotrophs to successfully cause secondary infection (infection spread from an initially infected plant to the nearby uninfected plants) is to effectively utilize nutrients released from hosts towards building up a large population before other saprophytes come. In this study, we observed that the necrotrophic pathogen Dickeya dadantii exhibited heterogeneity in bacterial cell length in an isogenic population during infection of potato tuber. While some cells were regular rod-shape (<10μm), the rest elongated into filamentous cells (>10μm). Short cells tended to occur at the interface of healthy and diseased tissues, during the early stage of infection when active attacking and killing is occurring, while filamentous cells tended to form at a later stage of infection. Short cells expressed all necessary virulence factors and motility, whereas filamentous cells did not engage in virulence, were non-mobile and more sensitive to environmental stress. However, compared to the short cells, the filamentous cells displayed upregulated metabolic genes and increased growth, which may benefit the pathogens to build up a large population necessary for the secondary infection. The segregation of the two subpopulations was dependent on differential production of the alarmone guanosine tetraphosphate (ppGpp). When exposed to fresh tuber tissues or freestanding water, filamentous cells quickly transformed to short virulent cells. The pathogen adaptation of cell length heterogeneity identified in this study presents a model for how some necrotrophs balance virulence and vegetative growth to maximize fitness during infection.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2025

Microbiomes of frozen blood plasma samples reveal potential pathogens in wild birds and rodents

The lack of genomic data on pathogens from wildlife severely limits our ability to track transmission patterns and trace the origins of an outbreak. There are currently millions of wildlife samples in biobanks around the world, including blood samples. Blood has traditionally been viewed as a sterile environment in healthy individuals, but recent evidence suggests that this is not the case, especially for wild animals. Our goal was to determine whether frozen plasma samples can be surveyed using 16S sequencing to provide information about potential hosts for pathogens for a more complete understanding of disease systems. We sequenced blood plasma from wild North American deer mice ( Peromyscus maniculatus ) and American kestrels ( Falco sparverius ) that were cryogenically stored for 7 and 13 years, respectively, and compared two DNA extraction kits. The kestrel samples contained a very high number of reads that could not be identified to phylum compared to the mouse samples. The two kits differed in the phyla and genera that were detected, and the Zymo kit, which is optimized for plasma and serum, produced more high-quality reads for both kestrel and mouse samples. We identified several pathogenic genera, including Mycoplasma, Escherichia-Shigella , and Bartonella . Sequencing blood samples for pathogens could potentially have broad applications for identifying important reservoir hosts for pathogen transmission and provide a reduced set of species on which to follow up.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2017

Two single mutations in the fusion protein of Newcastle disease virus confer hemagglutinin-neuraminidase independent fusion promotion and attenuate the pathogenicity in chickens

The fusion (F) protein of Newcastle disease virus (NDV) affects viral infection and pathogenicity through mediating membrane fusion. Previously, we found NDV with increased fusogenic activity in which contained T458D or G459D mutation in the F protein. Here, we investigated the effects of these two mutations on viral infection, fusogenicity and pathogenicity. Syncytium formation assays indicated that T458D or G459D increased the F protein cleavage activity and enhanced cell fusion with or without the presence of HN protein. The T458D- or G459D-mutated NDV resulted in a decrease in virus replication or release from cells. The animal study showed that the pathogenicity of the mutated NDVs was attenuated in chickens. These results indicate that these two single mutations in F altered or diminished the requirement of HN for promoting membrane fusion. The increased fusogenic activity may disrupt the cellular machinery and consequently decrease the virus replication and pathogenicity in chickens. - Highlights: • T458D or G459D mutation in the F protein enhanced the fuosogenicity with HN. • T458D or G459D mutation in the F protein promoted the fusion independently. • The growth of the T458D or G459D mutated virus was decreased in the cells. • The pathogenicity of the T458D or G459D mutated virus was attenuated in chickens.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2020

Fecal microbiota transplant rescues mice from human pathogen mediated sepsis by restoring systemic immunity

Death due to sepsis remains a persistent threat to critically ill patients confined to the intensive care unit and is characterized by colonization with multi-drug-resistant healthcare-associated pathogens. Here we report that sepsis in mice caused by a defined four-member pathogen community isolated from a patient with lethal sepsis is associated with the systemic suppression of key elements of the host transcriptome required for pathogen clearance and decreased butyrate expression. More specifically, these pathogens directly suppress interferon regulatory factor 3. Fecal microbiota transplant (FMT) reverses the course of otherwise lethal sepsis by enhancing pathogen clearance via the restoration of host immunity in an interferon regulatory factor 3-dependent manner. This protective effect is linked to the expansion of butyrate-producing Bacteroidetes. Taken together these results suggest that fecal microbiota transplantation may be a treatment option in sepsis associated with immunosuppression.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Transitions of foliar mycobiota community and transcriptome in response to pathogenic conifer needle interactions

Profiling the host–mycobiota interactions in healthy vs. diseased forest ecosystems helps understand the dynamics of understudied yet increasingly important threats to forest health that are emerging due to climate change. We analyzed the structural and functional changes of the mycobiota and the responses of Pinus contorta in the Lophodermella needle cast pathosystem through metabarcoding and metatranscriptomics. When needles transitioned from asymptomatic to symptomatic, dysbiosis of the mycobiota occurred, but with an enrichment of Lophodermella pathogens. Many pathogenicity-related genes were highly expressed by the mycobiota at the necrotrophic phase, showing an active pathogen response that are absent in asymptomatic needles. This study also revealed that Lophodermella spp. are members of a healthy needle mycobiota that have latent lifestyles suggesting that other pine needle pathogens may have similar biology. Interestingly, Pinus contorta upregulated defense genes in healthy needles, indicating response to fungal recognition, while a variety of biotic and abiotic stresses genes were activated in diseased needles. Further investigation to elucidate the possible antagonistic interplay of other biotic members leading to disease progression and/or suppression is warranted. This study provides insights into microbial interactions in non-model pathosystems and contributes to the development of new forest management strategies against emerging latent pathogens.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2018

Metal-free class Ie ribonucleotide reductase from pathogens initiates catalysis with a tyrosine-derived dihydroxyphenylalanine radical

All cells obtain 2'-deoxyribonucleotides for DNA synthesis through the activity of a ribonucleotide reductase (RNR). The class I RNRs found in humans and pathogenic bacteria differ in ( i ) use of Fe(II), Mn(II), or both for activation of the dinuclear-metallocofactor subunit, β; ( ii ) reaction of the reduced dimetal center with dioxygen or superoxide for this activation; ( iii ) requirement (or lack thereof) for a flavoprotein activase, NrdI, to provide the superoxide from O 2 ; and ( iv ) use of either a stable tyrosyl radical or a high-valent dimetal cluster to initiate each turnover by oxidizing a cysteine residue in the α subunit to a radical (Cys•). The use of manganese by bacterial class I, subclass b-d RNRs, which contrasts with the exclusive use of iron by the eukaryotic Ia enzymes, appears to be a countermeasure of certain pathogens against iron deprivation imposed by their hosts. Here, we report a metal-free type of class I RNR (subclass e) from two human pathogens. The Cys• in its α subunit is generated by a stable, tyrosine-derived dihydroxyphenylalanine radical (DOPA•) in β. The three-electron oxidation producing DOPA• occurs in Escherichia coli only if the β is coexpressed with the NrdI activase encoded adjacently in the pathogen genome. We conclude the independence of this new RNR from transition metals, or the requirement for a single metal ion only transiently for activation, may afford the pathogens an even more potent countermeasure against transition metal-directed innate immunity.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2018

Differential roles of melatonin in plant‐host resistance and pathogen suppression in cucurbits

Abstract Since the 1950s, research on the animal neurohormone, melatonin, has focused on its multiregulatory effect on patients suffering from insomnia, cancer, and Alzheimer’s disease. In plants, melatonin plays major role in plant growth and development, and is inducible in response to diverse biotic and abiotic stresses. However, studies on the direct role of melatonin in disease suppression and as a signaling molecule in host‐pathogen defense mechanism are lacking. This study provides insight on the predicted biosynthetic pathway of melatonin in watermelon ( Citrullus lanatus ), and how application of melatonin, an environmental‐friendly immune inducer, can boost plant immunity and suppress pathogen growth where fungicide resistance and lack of genetic resistance are major problems. We evaluated the effect of spray‐applied melatonin and also transformed watermelon plants with the melatonin biosynthetic gene SNAT (serotonin N‐acetyltransferase) to determine the role of melatonin in plant defense. Increased melatonin levels in plants were found to boost resistance against the foliar pathogen Podosphaera xanthii (powdery mildew), and the soil‐borne oomycete Phytophthora capsici in watermelon and other cucurbits. Further, transcriptomic data on melatonin‐sprayed (1 mmol/L) watermelon leaves suggest that melatonin alters the expression of genes involved in both PAMP ‐mediated (pathogen‐associated molecular pattern) and ETI ‐mediated (effector‐triggered immunity) defenses. Twenty‐seven upregulated genes were associated with constitutive defense as well as initial priming of the melatonin‐induced plant resistance response. Our results indicate that developing strategies to increase melatonin levels in specialty crops such as watermelon can lead to resistance against diverse filamentous pathogens.

Mandal, Mihir Kumar↗
DOE OSTI2019

Show me your secret(ed) weapons: a multifaceted approach reveals a wide arsenal of type III‐secreted effectors in the cucurbit pathogenic bacterium Acidovorax citrulli and novel effectors in the Acidovorax genus

Summary The cucurbit pathogenic bacterium Acidovorax citrulli requires a functional type III secretion system (T3SS) for pathogenicity. In this bacterium, as with Xanthomonas and Ralstonia spp . , an AraC‐type transcriptional regulator, HrpX, regulates expression of genes encoding T3SS components and type III‐secreted effectors (T3Es) . The annotation of a sequenced A. citrulli strain revealed 11 T3E genes. Assuming that this could be an underestimation, we aimed to uncover the T3E arsenal of the A. citrulli model strain, M6. Thorough sequence analysis revealed 51 M6 genes whose products are similar to known T3Es. Furthermore, we combined machine learning and transcriptomics to identify novel T3Es. The machine‐learning approach ranked all A. citrulli M6 genes according to their propensity to encode T3Es. RNA‐Seq revealed differential gene expression between wild‐type M6 and a mutant defective in HrpX: 159 and 28 genes showed significantly reduced and increased expression in the mutant relative to wild‐type M6, respectively. Data combined from these approaches led to the identification of seven novel T3E candidates that were further validated using a T3SS‐dependent translocation assay. These T3E genes encode hypothetical proteins that seem to be restricted to plant pathogenic Acidovorax species. Transient expression in Nicotiana benthamiana revealed that two of these T3Es localize to the cell nucleus and one interacts with the endoplasmic reticulum. This study places A. citrulli among the ‘richest’ bacterial pathogens in terms of T3E cargo. It also revealed novel T3Es that appear to be involved in the pathoadaptive evolution of plant pathogenic Acidovorax species.

Jiménez‐Guerrero, Irene↗
DOE OSTI2026

A conserved glycan motif induces broadly reactive functional antibodies against the zoonotic pathogen Streptococcus suis

Streptococcus suis is a largely neglected but emerging bacterial zoonotic pathogen of global concern for animal welfare, antibiotic resistance development, and human health. No effective vaccines are now available. Here, we identified and characterized the function and structure of two cell wall polysaccharide variants in pathogenic S. suis strains using genetic deletion and (heterologous) complementation, lectin staining, glycan composition analysis, and specialized NMR spectroscopy. Both glycan variants were anionic polymers that differed in the presence of glucose in the side chain as a result of allelic variation in a glycosyltransferase gene. Deletion of this variable glycosyltransferase revealed an identical glycan “core” and affected S. suis morphology and lysozyme resistance. Immunization of pigs with this core domain elicited antibodies that recognized antigenically diverse pathogenic S. suis strains and induced complement deposition on encapsulated pathogenic S. suis strains. This study provides valuable insights for developing next-generation glycoconjugate vaccines, whereby a single-glycan target could protect against the emerging zoonotic pathogen S. suis.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

Membership and Behavior of Ultra-Low-Diversity Pathogen Communities Present in the Gut of Humans during Prolonged Critical Illness

We analyzed the 16S rRNA amplicon composition in fecal samples of selected patients during their prolonged stay in an intensive care unit (ICU) and observed the emergence of ultra-low-diversity communities (1 to 4 bacterial taxa) in 30% of the patients. Bacteria associated with the genera Enterococcus and Staphylococcus and the family Enterobacteriaceae comprised the majority of these communities. The composition of cultured species from stool samples correlated to the 16S rRNA analysis and additionally revealed the emergence of Candida albicans and Candida glabrata in ~75% of cases. Four of 14 ICU patients harbored 2-member pathogen communities consisting of one Candida taxon and one bacterial taxon. Bacterial members displayed a high degree of resistance to multiple antibiotics. The virulence potential of the 2-member communities was examined in C. elegans during nutrient deprivation and exposure to opioids in order to mimic local conditions in the gut during critical illness. Under conditions of nutrient deprivation, the bacterial members attenuated the virulence of fungal members, leading to a “commensal lifestyle.” However, exposure to opioids led to a breakdown in this commensalism in 2 of the ultra-low-diversity communities. Application of a novel antivirulence agent (phosphate-polyethylene glycol [Pi-PEG]) that creates local phosphate abundance prevented opioid-induced virulence among these pathogen communities, thus rescuing the commensal lifestyle. To conclude, the gut microflora in critically ill patients can consist of ultra-low-diversity communities of multidrug-resistant pathogenic microbes. Local environmental conditions in gut may direct pathogen communities to adapt to either a commensal style or a pathogenic style.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2019

Multi-omics Signature of Candida auris , an Emerging and Multidrug-Resistant Pathogen

Candida auris is a recently described pathogenic fungus that is causing invasive outbreaks on all continents. The fungus is of high concern given the numbers of multidrug-resistant strains that have been isolated in distinct sites across the globe. The fact that its diagnosis is still problematic suggests that the spreading of the pathogen remains underestimated. Notably, the molecular mechanisms of virulence and antifungal resistance employed by this new species are largely unknown. In the present work, we compared two clinical isolates of C. auris with distinct drug susceptibility profiles and a Candida albicans reference strain using a multi-omics approach. Our results show that, despite the distinct drug resistance profile, both C. auris isolates appear to be very similar, albeit with a few notable differences. However, compared to C. albicans both C. auris isolates have major differences regarding their carbon utilization and downstream lipid and protein content, suggesting a multifactorial mechanism of drug resistance. The molecular profile displayed by C. auris helps to explain the antifungal resistance and virulence phenotypes of this new emerging pathogen. Candida auris was first described in Japan in 2009 and has now been the cause of significant outbreaks across the globe. The high number of isolates that are resistant to one or more antifungals, as well as the high mortality rates from patients with bloodstream infections, has attracted the attention of the medical mycology, infectious disease, and public health communities to this pathogenic fungus. In the current work, we performed a broad multi-omics approach on two clinical isolates isolated in New York, the most affected area in the United States and found that the omic profile of C. auris differs significantly from C. albicans . In addition to our insights into C. auris carbon utilization and lipid and protein content, we believe that the availability of these data will enhance our ability to combat this rapidly emerging pathogenic yeast.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2016

The genome of the emerging barley pathogen Ramularia collo-cygni

Ramularia collo-cygni is a newly important, foliar fungal pathogen of barley that causes the disease Ramularia leaf spot. The fungus exhibits a prolonged endophytic growth stage before switching life habit to become an aggressive, necrotrophic pathogen that causes significant losses to green leaf area and hence grain yield and quality. The R. collo-cygni genome was sequenced using a combination of Illumina and Roche 454 technologies. The draft assembly of 30.3 Mb contained 11,617 predicted gene models. Our phylogenomic analysis confirmed the classification of this ascomycete fungus within the family Mycosphaerellaceae, order Capnodiales of the class Dothideomycetes. A predicted secretome comprising 1053 proteins included redoxrelated enzymes and carbohydrate-modifying enzymes and proteases. The relative paucity of plant cell wall degrading enzyme genes may be associated with the stealth pathogenesis characteristic of plant pathogens from the Mycosphaerellaceae. A large number of genes associated with secondary metabolite production, including homologs of toxin biosynthesis genes found in other Dothideomycete plant pathogens, were identified. The genome sequence of R. collo-cygni provides a framework for understanding the genetic basis of pathogenesis in this important emerging pathogen. The reduced complement of carbohydrate-degrading enzyme genes is likely to reflect a strategy to avoid detection by host defences during its prolonged asymptomatic growth. Of particular interest will be the analysis of R. collo-cygni gene expression during interactions with the host barley, to understand what triggers this fungus to switch from being a benign endophyte to an aggressive necrotroph.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Escalation in the host-pathogen arms race: A host resistance response corresponds to a heightened bacterial virulence response

The zig-zag model of host-pathogen interaction describes the relative strength of defense response across a spectrum of pathogen-induced plant phenotypes. A stronger defense response results in increased resistance. Here, we investigate the strength of pathogen virulence during disease and place these findings in the context of the zig-zag model. Xanthomonas vasicola pv. holcicola ( Xvh ) causes sorghum bacterial leaf streak. Despite being widespread, this disease has not been described in detail at the molecular level. We divided diverse sorghum genotypes into three groups based on disease symptoms: water-soaked lesions, red lesions, and resistance. Bacterial growth assays confirmed that these three phenotypes represent a range of resistance and susceptibility. To simultaneously reveal defense and virulence responses across the spectrum of disease phenotypes, we performed dual RNA-seq on Xvh -infected sorghum. Consistent with the zig-zag model, the expression of plant defense-related genes was strongest in the resistance interaction. Surprisingly, bacterial virulence genes related to the type III secretion system (T3SS) and type III effectors (T3Es) were also most highly expressed in the resistance interaction. This expression pattern was observed at multiple time points within the sorghum- Xvh pathosystem. Further, a similar expression pattern was observed in Arabidopsis infected with Pseudomonas syringae for effector-triggered immunity via AvrRps4 but not AvrRpt2. Specific metabolites were able to repress the Xvh virulence response in vitro and in planta suggesting a possible signaling mechanism. Taken together, these findings reveal multiple permutations of the continually evolving host-pathogen arms race from the perspective of host defense and pathogen virulence responses.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Isolation, Characterization, and Pathogenicity of Two Pseudomonas syringae Pathovars from Populus trichocarpa Seeds

Pseudomonas syringae is a ubiquitous plant pathogen, infecting both woody and herbaceous plants and resulting in devastating agricultural crop losses. Characterized by a remarkable specificity for plant hosts, P. syringae pathovars utilize a number of virulence factors including the type III secretion system and effector proteins to elicit disease in a particular host species. Here, two Pseudomonas syringae strains were isolated from diseased Populustrichocarpa seeds. The pathovars were capable of inhibiting poplar seed germination and were selective for the Populus genus. Sequencing of the newly described organisms revealed similarity to phylogroup II pathogens and genomic regions associated with woody host-associated plant pathogens, as well as genes for specific virulence factors. The host response to infection, as revealed through metabolomics, is the induction of the stress response through the accumulation of higher-order salicylates. Combined with necrosis on leaf surfaces, the plant appears to quickly respond by isolating infected tissues and mounting an anti-inflammatory defense. This study improves our understanding of the initial host response to epiphytic pathogens in Populus and provides a new model system for studying the effects of a bacterial pathogen on a woody host plant in which both organisms are fully genetically sequenced.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

High-throughput functional trait testing for bacterial pathogens

Functional traits are characteristics that affect the fitness and metabolic function of a microorganism. There is growing interest in using high-throughput methods to characterize bacterial pathogens based on functional virulence traits. Traditional methods that phenotype a single organism for a single virulence trait can be time consuming and labor intensive. Alternatively, machine learning of whole-genome sequences (WGS) has shown some success in predicting virulence. However, relying solely on WGS can miss functional traits, particularly for organisms lacking classical virulence factors. We propose that high-throughput assays for functional virulence trait identification should become a prominent method of characterizing bacterial pathogens on a population scale. This work is critical as we move from compiling lists of bacterial species associated with disease to pathogen-agnostic approaches capable of detecting novel microbes. We discuss six key areas of functional trait testing and how advancing high-throughput methods could provide a greater understanding of pathogens.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2016

Challenges and priorities for modelling livestock health and pathogens in the context of climate change

Climate change has the potential to impair livestock health, with consequences for animal welfare, productivity, greenhouse gas emissions, and human livelihoods and health. Modelling has an important role in assessing the impacts of climate change on livestock systems and the efficacy of potential adaptation strategies, to support decision making for more efficient, resilient and sustainable production. However, a coherent set of challenges and research priorities for modelling livestock health and pathogens under climate change has not previously been available. To identify such challenges and priorities, researchers from across Europe were engaged in a horizon-scanning study, involving workshop and questionnaire based exercises and focussed literature reviews. Eighteen key challenges were identified and grouped into six categories based on subject-specific and capacity building requirements. Across a number of challenges, the need for inventories relating model types to different applications (e.g. the pathogen species, region, scale of focus and purpose to which they can be applied) was identified, in order to identify gaps in capability in relation to the impacts of climate change on animal health. The need for collaboration and learning across disciplines was highlighted in several challenges, e.g. to better understand and model complex ecological interactions between pathogens, vectors, wildlife hosts and livestock in the context of climate change. Collaboration between socio-economic and biophysical disciplines was seen as important for better engagement with stakeholders and for improved modelling of the costs and benefits of poor livestock health. The need for more comprehensive validation of empirical relationships, for harmonising terminology and measurements, and for building capacity for under-researched nations, systems and health problems indicated the importance of joined up approaches across nations. The challenges and priorities identified can help focus the development of modelling capacity and future research structures in this vital field. Well-funded networks capable of managing the long-term development of shared resources are required in order to create a cohesive modelling community equipped to tackle the complex challenges of climate change. - Highlights: • Experts identified challenges for health and pathogen modelling under climate change. • Eighteen key challenges and associated research priorities were identified. • Increasing capacity will require improved organisation and sharing knowledge. • Better communication across the diverse topics and approaches in this field is needed.

54 ENVIRONMENTAL SCIENCES↗