Contrasting long-term dynamics of antimicrobial resistance and virulence plasmids in Salmonella Typhimurium from animals.

Plasmids are mobile elements that can carry genes encoding traits of clinical concern, including antimicrobial resistance (AMR) and virulence. Population-level studies of Enterobacterales, including Escherichia coli, Shigella and Klebsiella, indicate that plasmids are important drivers of lineage expansions and dissemination of AMR genes. Salmonella Typhimurium is the second most common cause of salmonellosis in humans and livestock in the UK and Europe. The long-term dynamics of plasmids between S. Typhimurium were investigated using isolates collected through national surveillance of animals in England and Wales over a 25-year period. The population structure of S. Typhimurium and its virulence plasmid (where present) were inferred through phylogenetic analyses using whole-genome sequence data for 496 isolates. Antimicrobial resistance genes and plasmid markers were detected in silico. Phenotypic plasmid characterization, using the Kado and Liu method, was used to confirm the number and size of plasmids. The differences in AMR and plasmids between clades were striking, with livestock clades more likely to carry one or more AMR plasmid and be multi-drug-resistant compared to clades associated with wildlife and companion animals. Multiple small non-AMR plasmids were distributed across clades. However, all hybrid AMR-virulence plasmids and most AMR plasmids were highly clade-associated and persisted over decades, with minimal evidence of horizontal transfer between clades. This contrasts with the role of plasmids in the short-term dissemination of AMR between diverse strains in other Enterobacterales in high-antimicrobial-use settings, with implications for predicting plasmid dissemination amongst S. Typhimurium.

Automated reanalysis application to assist in detecting novel gene-disease associations after genome sequencing.

PURPOSE: This study aimed to investigate whether a bioinformatics application can streamline genome reanalysis and yield new diagnoses for patients with rare diseases. METHODS: We developed TierUp to identify variants in new disease genes for unresolved rare disease cases recruited to the 100,000 Genomes Project, all of whom underwent genome sequencing. TierUp uses the NHS Genomic Medicine Service bioinformatics infrastructure by securely accessing case details from the Clinical Interpretation Portal application programming interface and by querying the curated PanelApp database for novel gene-disease associations. We applied TierUp to 948 cases, and a subset of variants were reclassified according to the American College of Medical Genetics and Genomics/Association of Molecular Pathology guidelines. RESULTS: A rare form of spondylometaphyseal dysplasia was diagnosed through TierUp reanalysis, and an additional 4 variants have been reported to date. From a total of 564,441 variants across patients, TierUp highlighted 410 variants present in novel disease genes in under 77 minutes, successfully expediting an important reanalysis strategy. CONCLUSION: TierUp supports claims that automation can reduce the time taken to reanalyze variants and increase the diagnostic yield from molecular testing. Clinical services should leverage bioinformatics expertise to develop tools that enable routine reanalysis. In addition, services must also explore the ethical, legal, and health economic considerations raised by automation.

Bradyrhizobium Inoculants Enhance Grain Yields of Soybean and Cowpea in Northern Ghana.

This study evaluated the symbiotic effectiveness and economic evaluation of Rhizobium inoculants with the objective of recommending the most effective inoculant strain for soybean and cowpea production in Northern Ghana. Field experiments were established in three locations using randomized complete block design with five blocks. A total of four treatments (Legumefix, Biofix, 100 kg N ha-1 and uninoculated control for soybean and BR 3267, BR 3262, 100 kg N ha-1 and uninoculated control for cowpea) were applied. At Nyankpala, inoculation of soybean with Legumefix and Biofix led to significant (P < 0.05) increases in nodule number (90-118%), nodule dry weight (>two-folds), and grain yield (12-19%) relative to the control. The Biofix effect on soybean grain yield was 1.5-fold of Legumefix. Similarly, inoculation of cowpea with BR 3262 and BR 3267 significantly (P < 0.05) increased nodule number (41-68%), nodule dry weight (45-65%), and grain yield (11-38%) relative to the control. Strain BR 3267 performed consistently (>two-folds) better than BR 3262 on grain yield. At Nyagli, there was no significant effect of inoculation on cowpea. Wilks lambda values (0.067, 0.039; P = 0.00) indicated that 93.3 and 96.1% of the variations observed in soybean and cowpea, respectively, were due to the applied inoculants. Biofix and BR 3267 were economically profitable with VCR ratio of 8.7 and 4.6, respectively. Based on grain yield and economic returns observed, Biofix and BR 3267 can be recommended in Nyankpala for inoculation of soybean and cowpea, respectively.