Complete genome sequence of Salmonella enterica serovar Typhimurium U288

Salmonella enterica serovar Typhimurium U288 has firmly established itself within the United Kingdom pig production industry. The prevalence of this highly pathogenic multidrug-resistant serovar at such a critical point in the food chain is therefore of great concern. To enhance our understanding of this microorganism, whole-genome and plasmid sequencing was performed

Salmonella Typhimurium-specific bacteriophage ΦSH19 and the origins of species specificity in the Vi01-like phage family

<p>Abstract</p> <p>Background</p> <p>Whole genome sequencing of bacteriophages suitable for biocontrol of pathogens in food products is a pre-requisite to any phage-based intervention procedure. Trials involving the biosanitization of <it>Salmonella </it>Typhimurium in the pig production environment identified one such candidate, ΦSH19.</p> <p>Results</p> <p>This phage was sequenced and analysis of its 157,785 bp circular dsDNA genome revealed a number of interesting features. ΦSH19 constitutes another member of the recently-proposed <it>Myoviridae </it>Vi01-like family of phages, containing <it>S</it>. Typhi-specific Vi01 and <it>Shigella</it>-specific SboM-AG3. At the nucleotide level ΦSH19 is highly similar to phage Vi01 (80-98% pairwise identity over the length of the genome), with the major differences lying in the region associated with host-range determination. Analyses of the proteins encoded within this region by ΦSH19 revealed a cluster of three putative tail spikes. Of the three tail spikes, two have protein domains associated with the pectate lyase family of proteins (Tsp2) and P22 tail spike family (Tsp3) with the prospect that these enable <it>Salmonella </it>O antigen degradation. Tail spike proteins of Vi01 and SboM-AG3 are predicted to contain conserved right-handed parallel β-helical structures but the internal protein domains are varied allowing different host specificities.</p> <p>Conclusions</p> <p>The addition or exchange of tail spike protein modules is a major contributor to host range determination in the Vi01-like phage family.</p

Genome Dynamics of Campylobacter jejuni in Response to Bacteriophage Predation

Campylobacter jejuni is a leading cause of food-borne illness. Although a natural reservoir of the pathogen is domestic poultry, the degree of genomic diversity exhibited by the species limits the application of epidemiological methods to trace specific infection sources. Bacteriophage predation is a common burden placed upon C. jejuni populations in the avian gut, and we show that amongst C. jejuni that survive bacteriophage predation in broiler chickens are bacteriophage-resistant types that display clear evidence of genomic rearrangements. These rearrangements were identified as intra-genomic inversions between Mu-like prophage DNA sequences to invert genomic segments up to 590 kb in size, the equivalent of one-third of the genome. The resulting strains exhibit three clear phenotypes: resistance to infection by virulent bacteriophage, inefficient colonisation of the broiler chicken intestine, and the production of infectious bacteriophage CampMu. These genotypes were recovered from chickens in the presence of virulent bacteriophage but not in vitro. Reintroduction of these strains into chickens in the absence of bacteriophage results in further genomic rearrangements at the same locations, leading to reversion to bacteriophage sensitivity and colonisation proficiency. These findings indicate a previously unsuspected method by which C. jejuni can generate genomic diversity associated with selective phenotypes. Genomic instability of C. jejuni in the avian gut has been adopted as a mechanism to temporarily survive bacteriophage predation and subsequent competition for resources, and would suggest that C. jejuni exists in vivo as families of related meta-genomes generated to survive local environmental pressures

The complete plasmid sequences of Salmonella enterica serovar Typhimurium U288.

Salmonella enterica Serovar Typhimurium U288 is an emerging pathogen of pigs. The strain contains three plasmids of diverse origin that encode traits that are of concern for food security and safety, these include antibiotic resistant determinants, an array of functions that can modify cell physiology and permit genetic mobility. At 148,711 bp, pSTU288-1 appears to be a hybrid plasmid containing a conglomerate of genes found in pSLT of S. Typhimurium LT2, coupled with a mosaic of horizontally-acquired elements. Class I integron containing gene cassettes conferring resistance against clinically important antibiotics and compounds are present in pSTU288-1. A curious feature of the plasmid involves the deletion of two genes encoded in the Salmonella plasmid virulence operon (spvR and spvA) following the insertion of a tnpA IS26-like element coupled to a blaTEM gene. The spv operon is considered to be a major plasmid-encoded Salmonella virulence factor that is essential for the intracellular lifecycle. The loss of the positive regulator SpvR may impact on the pathogenesis of S. Typhimurium U288. A second 11,067 bp plasmid designated pSTU288-2 contains further antibiotic resistance determinants, as well as replication and mobilization genes. Finally, a small 4675 bp plasmid pSTU288-3 was identified containing mobilization genes and a pleD-like G-G-D/E-E-F conserved domain protein that modulate intracellular levels of cyclic di-GMP, and are associated with motile to sessile transitions in growth

Functionalized Copper Nanoparticles with Gold Nanoclusters: Part I. Highly Selective Electrosynthesis of Hydrogen Peroxide

© 2023 The Authors. Published by American Chemical Society. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/Copper nanoparticles (CuNPs) and gold nanoclusters (AuNCs) show a high catalytic performance in generating hydrogen peroxide (H2O2), a property that can be exploited to kill disease-causing microbes and to carry carbon-free energy. Some combinations of NPs/NCs can generate synergistic effects to produce stronger antiseptics, such as H2O2 or other reactive oxygen species (ROS). Herein, we demonstrate a novel facile AuNC surface decoration method on the surfaces of CuNPs using galvanic displacement. The Cu–Au bimetallic NPs presented a high selective production of H2O2 via a two-electron (2e–) oxygen reduction reaction (ORR). Their physicochemical analyses were conducted by scanning electron microscopy (SEM), transmitting electron microscopy (TEM), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS). With the optimized Cu–Au1.5NPs showing their particle sizes averaged in 53.8 nm, their electrochemical analysis indicated that the pristine AuNC structure exhibited the highest 2e– selectivity in ORR, the CuNPs presented the weakest 2e– selectivity, and the optimized Cu–Au1.5NPs exhibited a high 2e– selectivity of 95% for H2O2 production, along with excellent catalytic activity and durability. The optimized Cu–Au1.5NPs demonstrated a novel pathway to balance the cost and catalytic performance through the appropriate combination of metal NPs/NCs.Peer reviewe

Evidence for a lineage of virulent bacteriophages that target Campylobacter.

BACKGROUND: Our understanding of the dynamics of genome stability versus gene flux within bacteriophage lineages is limited. Recently, there has been a renewed interest in the use of bacteriophages as 'therapeutic' agents; a prerequisite for their use in such therapies is a thorough understanding of their genetic complement, genome stability and their ecology to avoid the dissemination or mobilisation of phage or bacterial virulence and toxin genes. Campylobacter, a food-borne pathogen, is one of the organisms for which the use of bacteriophage is being considered to reduce human exposure to this organism. RESULTS: Sequencing and genome analysis was performed for two Campylobacter bacteriophages. The genomes were extremely similar at the nucleotide level (> or = 96%) with most differences accounted for by novel insertion sequences, DNA methylases and an approximately 10 kb contiguous region of metabolic genes that were dissimilar at the sequence level but similar in gene function between the two phages. Both bacteriophages contained a large number of radical S-adenosylmethionine (SAM) genes, presumably involved in boosting host metabolism during infection, as well as evidence that many genes had been acquired from a wide range of bacterial species. Further bacteriophages, from the UK Campylobacter typing set, were screened for the presence of bacteriophage structural genes, DNA methylases, mobile genetic elements and regulatory genes identified from the genome sequences. The results indicate that many of these bacteriophages are related, with 10 out of 15 showing some relationship to the sequenced genomes. CONCLUSIONS: Two large virulent Campylobacter bacteriophages were found to show very high levels of sequence conservation despite separation in time and place of isolation. The bacteriophages show adaptations to their host and possess genes that may enhance Campylobacter metabolism, potentially advantaging both the bacteriophage and its host. Genetic conservation has been shown to extend to other Campylobacter bacteriophages, forming a highly conserved lineage of bacteriophages that predate upon campylobacters and indicating that highly adapted bacteriophage genomes can be stable over prolonged periods of time

The Arginine Methyltransferase Carm1 is Necessary for Heart Development

To discover genes implicated in human congenital disorders, we performed ENU mutagenesis in the mouse and screened for mutations affecting embryonic development. In this work we report defects of heart development in mice homozygous for a mutation of Coactivator-associated Arginine Methyltransferase 1 (Carm1). While Carm1 has been extensively studied, it has never been previously associated with a role in heart development. Phenotype analysis combining histology and micro-computed tomography (micro-CT) imaging shows a range of cardiac defects. Most notably, many affected mid-gestation embryos appear to have cardiac rupture and hemorrhaging in the thorax. Mice that survive to late gestation show a variety of cardiac defects, including Ventricular Septal Defects (VSDs), Double Outlet Right Ventricle (DORV), and Persistent Truncus Arteriosus (PTA). Transcriptome analyses of the mutant embryos by mRNA-seq reveal the perturbation of several genes involved in cardiac morphogenesis and muscle development and function. In addition, we observe the mis-localization of cardiac neural crest cells at E12.5 in the outflow tract. The cardiac phenotype of Carm1 mutant embryos is similar to that of Pax3 null mutants, and PAX3 is a putative target of CARM1. However, our analysis does not support the hypothesis that developmental defects in Carm1 mutant embryos are primarily due to a functional defect of PAX3

Sport events and human rights: positive promotion or negative erosion?

© 2015 Taylor & Francis. In this paper, we build upon recent scholarship on sport event legacies to identify, categorise, and describe the key processes underpinning sport event interactions with human rights (HR). It develops a simple, representative model to illustrate the points where sport events bisect with HR and considers what factors can modify these impacts. The development of this model is based on a meta-review of literature and examination of case studies. It is clear from our analysis that sport events are malleable, symbolic, and political occurrences that can be positioned to provide evidence and support of benefice or harm to the cause of HR. The model also provides a nuanced approach to consider how sport event organisers may begin to think about the tactics and strategies that might be employed, and how they might leverage HR through their sport event. The model also indicates that HR, being similarly malleable political tools, are paradoxical in application in the sport event context and consequently cannot be assumed to be taken-for-granted as event outcomes or outputs

Homologous recombination deficiency in newly diagnosed FIGO stage III/IV high-grade epithelial ovarian cancer: a multi-national observational study

OBJECTIVE: Olaparib plus bevacizumab maintenance therapy improves survival outcomes in women with newly diagnosed, advanced, high-grade ovarian cancer with a deficiency in homologous recombination. We report data from the first year of routine homologous recombination deficiency testing in the National Health Service (NHS) in England, Wales, and Northern Ireland between April 2021 and April 2022. METHODS: The Myriad myChoice companion diagnostic was used to test DNA extracted from formalin-fixed, paraffin-embedded tumor tissue in women with newly diagnosed International Federation of Gynecology and Obstetrics (FIGO) stage III/IV high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer. Tumors with homologous recombination deficiency were those with a BRCA1/2 mutation and/or a Genomic Instability Score (GIS) ≥42. Testing was coordinated by the NHS Genomic Laboratory Hub network. RESULTS: The myChoice assay was performed on 2829 tumors. Of these, 2474 (87%) and 2178 (77%) successfully underwent BRCA1/2 and GIS testing, respectively. All complete and partial assay failures occurred due to low tumor cellularity and/or low tumor DNA yield. 385 tumors (16%) contained a BRCA1/2 mutation and 814 (37%) had a GIS ≥42. Tumors with a GIS ≥42 were more likely to be BRCA1/2 wild-type (n=510) than BRCA1/2 mutant (n=304). The distribution of GIS was bimodal, with BRCA1/2 mutant tumors having a higher mean score than BRCA1/2 wild-type tumors (61 vs 33, respectively, χ2 test p<0.0001). CONCLUSION: This is the largest real-world evaluation of homologous recombination deficiency testing in newly diagnosed FIGO stage III/IV high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer. It is important to select tumor tissue with adequate tumor content and quality to reduce the risk of assay failure. The rapid uptake of testing across England, Wales, and Northern Ireland demonstrates the power of centralized NHS funding, center specialization, and the NHS Genomic Laboratory Hub network