the impact of stakeholder decision-making on antimicrobial resistance evolution.

Antimicrobial resistance poses one of the greatest and most imminent threats to global health, environment and food security, for which an urgent response is mandated. Evolutionary approaches to tackling the crisis tend to focus on proximate issues including the mechanisms and pathways to resistance, with associated calls to action for infection control and antimicrobial stewardship. This is of clear benefit but overlooks the fundamental influence of policy and stakeholder decision-making on resistance evolution.

Observational study of antibiotic prescribing patterns by age and sex in primary care in England: why we need to take this variation into account to evaluate antibiotic stewardship and predict AMR variation.

Background: The drivers of antimicrobial resistance (AMR) likely vary substantially by different demographics. However, few complete, open, national detailed data exist on how antibiotic use (ABU) varies by both age and sex. Here, we aimed to describe the variation in ABU and consider how these age- and sex-specific patterns influence targets and methods for AMR control.

Antimicrobial drug pricing.

Despite the constant development of antimicrobial resistance (AMR), few new antimicrobials are currently becoming available clinically. Alternative approaches, such as different mechanisms to fund their use, are being explored to encourage development of new antimicrobials.

The trichothecene mycotoxin deoxynivalenol facilitates cell-to-cell invasion during wheat-tissue colonization by Fusarium graminearum.

Fusarium head blight disease on small-grain cereals is primarily caused by the ascomycete fungal pathogen Fusarium graminearum. Infection of floral spike tissues is characterized by the biosynthesis and secretion of potent trichothecene mycotoxins, of which deoxynivalenol (DON) is widely reported due to its negative impacts on grain quality and consumer safety. The TRI5 gene encodes an essential enzyme in the DON biosynthesis pathway and the single gene deletion mutant, ΔTri5, is widely reported to restrict disease progression to the inoculated spikelet.

Antimicrobial stewardship markers and healthcare-associated pneumonia threshold criteria in UK hospitals: analysis of the MicroGuide application.

Background: To address antimicrobial resistance, antimicrobial stewardship (AMS) principles must be implemented and adhered to. Clinical decision aids such as the MicroGuide app are an important part of these efforts. We sought to evaluate the consistency of core AMS information and the diversity of classification thresholds for healthcare-associated pneumonia (HAP) in the MicroGuide app.

An Insurance Value Modeling Approach That Captures the Wider Value of a Novel Antimicrobial to Health Systems, Patients, and the Population.

Traditional health economic evaluations of antimicrobials currently underestimate their value to wider society. They can be supplemented by additional value elements including insurance value, which captures the value of an antimicrobial in preventing or mitigating impacts of adverse risk events. Despite being commonplace in other sectors, constituents of the impacts and approaches for estimating insurance value have not been investigated.

Fungal plant pathogen "mutagenomics" reveals tagged and untagged mutations in and identifies SSK2 as key morphogenesis and stress-responsive virulence factor.

"Mutagenomics" is the combination of random mutagenesis, phenotypic screening, and whole-genome re-sequencing to uncover all tagged and untagged mutations linked with phenotypic changes in an organism. In this study, we performed a mutagenomics screen on the wheat pathogenic fungus for altered morphogenetic switching and stress sensitivity phenotypes using -mediated "random" T-DNA mutagenesis (ATMT). Biological screening identified four mutants which were strongly reduced in virulence on wheat.

Combined pangenomics and transcriptomics reveals core and redundant virulence processes in a rapidly evolving fungal plant pathogen.

Background: Studying genomic variation in rapidly evolving pathogens potentially enables identification of genes supporting their "core biology", being present, functional and expressed by all strains or "flexible biology", varying between strains. Genes supporting flexible biology may be considered to be "accessory", whilst the "core" gene set is likely to be important for common features of a pathogen species biology, including virulence on all host genotypes. The wheat-pathogenic fungus Zymoseptoria tritici represents one of the most rapidly evolving threats to global food security and was the focus of this study.

Reducing Dietary Acrylamide Exposure from Wheat Products through Crop Management and Imaging.

The nutritional safety of wheat-based food products is compromised by the presence of the processing contaminant acrylamide. Reduction of the key acrylamide precursor, free (soluble, non-protein) asparagine, in wheat grain can be achieved through crop management strategies, but such strategies have not been fully developed. We ran two field trials with 12 soft (biscuit) wheat varieties and different nitrogen, sulfur, potassium, and phosphorus fertilizer combinations.

Common Bean Subtelomeres Are Hot Spots of Recombination and Favor Resistance Gene Evolution.

Subtelomeres of most eukaryotes contain fast-evolving genes usually involved in adaptive processes. In common bean (), the anthracnose resistance () locus corresponds to a cluster of nucleotide-binding-site leucine-rich-repeat (NL) encoding sequences, the prevalent class of plant genes. To study the recent evolution of this gene cluster, we used a combination of sequence, genetic and cytogenetic comparative analyses between common bean genotypes from two distinct gene pools (Andean and Mesoamerican) that diverged 0.

Using decoys to expand the recognition specificity of a plant disease resistance protein.

Maintaining high crop yields in an environmentally sustainable manner requires the development of disease-resistant crop varieties. We describe a method to engineer disease resistance in plants by means of an endogenous disease resistance gene from Arabidopsis thaliana named RPS5, which encodes a nucleotide-binding leucine-rich repeat (NLR) protein. RPS5 is normally activated when a second host protein, PBS1, is cleaved by the pathogen-secreted protease AvrPphB.

Pseudomonas syringae Effector AvrPphB Suppresses AvrB-Induced Activation of RPM1 but Not AvrRpm1-Induced Activation.

The Pseudomonas syringae effector AvrB triggers a hypersensitive resistance response in Arabidopsis and soybean plants expressing the disease resistance (R) proteins RPM1 and Rpg1b, respectively. In Arabidopsis, AvrB induces RPM1-interacting protein kinase (RIPK) to phosphorylate a disease regulator known as RIN4, which subsequently activates RPM1-mediated defenses. Here, we show that AvrPphB can suppress activation of RPM1 by AvrB and this suppression is correlated with the cleavage of RIPK by AvrPphB.

Determining the GmRIN4 requirements of the soybean disease resistance proteins Rpg1b and Rpg1r using a nicotiana glutinosa-based agroinfiltration system.

Rpg1b and Rpg1r are soybean disease resistance (R) genes responsible for conferring resistance to Pseudomonas syringae strains expressing the effectors AvrB and AvrRpm1, respectively. The study of these cloned genes would be greatly facilitated by the availability of a suitable transient expression system. The commonly used Niciotiana benthamiana-based system is not suitable for studying Rpg1b and Rpg1r function, however, because expression of AvrB or AvrRpm1 alone induces a hypersensitive response (HR), indicating that N.

Evolutionary relationship of disease resistance genes in soybean and Arabidopsis specific for the Pseudomonas syringae effectors AvrB and AvrRpm1.

In Arabidopsis (Arabidopsis thaliana), the Pseudomonas syringae effector proteins AvrB and AvrRpm1 are both detected by the RESISTANCE TO PSEUDOMONAS MACULICOLA1 (RPM1) disease resistance (R) protein. By contrast, soybean (Glycine max) can distinguish between these effectors, with AvrB and AvrRpm1 being detected by the Resistance to Pseudomonas glycinea 1b (Rpg1b) and Rpg1r R proteins, respectively. We have been using these genes to investigate the evolution of R gene specificity and have previously identified RPM1 and Rpg1b.

Evolution of a complex disease resistance gene cluster in diploid Phaseolus and tetraploid Glycine.

We used a comparative genomics approach to investigate the evolution of a complex nucleotide-binding (NB)-leucine-rich repeat (LRR) gene cluster found in soybean (Glycine max) and common bean (Phaseolus vulgaris) that is associated with several disease resistance (R) genes of known function, including Rpg1b (for Resistance to Pseudomonas glycinea1b), an R gene effective against specific races of bacterial blight. Analysis of domains revealed that the amino-terminal coiled-coil (CC) domain, central nucleotide-binding domain (NB-ARC [for APAF1, Resistance genes, and CED4]), and carboxyl-terminal LRR domain have undergone distinct evolutionary paths. Sequence exchanges within the NB-ARC domain were rare.

Specific resistances against Pseudomonas syringae effectors AvrB and AvrRpm1 have evolved differently in common bean (Phaseolus vulgaris), soybean (Glycine max), and Arabidopsis thaliana.

*In plants, the evolution of specific resistance is poorly understood. Pseudomonas syringae effectors AvrB and AvrRpm1 are recognized by phylogenetically distinct resistance (R) proteins in Arabidopsis thaliana (Brassicaceae) and soybean (Glycine max, Fabaceae). In soybean, these resistances are encoded by two tightly linked R genes, Rpg1-b and Rpg1-r.

Replication of nonautonomous retroelements in soybean appears to be both recent and common.

Retrotransposons and their remnants often constitute more than 50% of higher plant genomes. Although extensively studied in monocot crops such as maize (Zea mays) and rice (Oryza sativa), the impact of retrotransposons on dicot crop genomes is not well documented. Here, we present an analysis of retrotransposons in soybean (Glycine max).

Differential accumulation of retroelements and diversification of NB-LRR disease resistance genes in duplicated regions following polyploidy in the ancestor of soybean.

The genomes of most, if not all, flowering plants have undergone whole genome duplication events during their evolution. The impact of such polyploidy events is poorly understood, as is the fate of most duplicated genes. We sequenced an approximately 1 million-bp region in soybean (Glycine max) centered on the Rpg1-b disease resistance gene and compared this region with a region duplicated 10 to 14 million years ago.

Diversification of non-TIR class NB-LRR genes in relation to whole-genome duplication events in Arabidopsis.

Arabidopsis thaliana is believed to have experienced at least two and possibly three whole-genome duplication events in its evolutionary history. In order to investigate the evolutionary relationships between these duplication events and diversification of disease resistance (R) genes, segmental-duplication events containing R genes belonging to the nucleotide binding-leucine rich repeat (NB-LRR) class were identified. Of 153 segmental-duplication events containing NB-LRR genes, only 22 contained NB-LRR genes in both members of the duplication pair, indicating a high frequency of NB-LRR gene loss after whole-genome duplication.

Convergent evolution of disease resistance gene specificity in two flowering plant families.

Plant disease resistance (R) genes that mediate recognition of the same pathogen determinant sometimes can be found in distantly related plant families. This observation implies that some R gene alleles may have been conserved throughout the diversification of land plants. To address this question, we have compared R genes from Glycine max (soybean), Rpg1-b, and Arabidopsis thaliana, RPM1, that mediate recognition of the same type III effector protein from Pseudomonas syringae, AvrB.