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Dekker, D.

Publications and source records attributed to Dekker, D..

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Genomic Insights into the Diversity, Antimicrobial Resistance, and Zoonotic Potential of Campylobacter fetus Across Diverse Hosts and Geographies

BackgroundCampylobacter fetus causes reproductive diseases in livestock and zoonotic infections in humans, especially in immunocompromised individuals. Despite its significance, its genomic characteristics are poorly understood. This study analyzed 114 publicly available C. fetus genomes to provide global insights into its genetic diversity, antimicrobial resistance (AMR) patterns, and zoonotic risk. ResultsA total of 32 distinct sequence types (STs), ranging from ST-1 to ST-74, were identified across 111 of the 114 C. fetus genomes, spanning six continents and diverse hosts (cattle, humans, sheep, and reptiles). ST-4 was the most prevalent (n = 45), followed by ST-3 (n = 8). A significant proportion (90.9%; n/N=40/44) of C. fetus subsp. venerealis (Cfv) and its biovar intermedius (Cfvi) were assigned to ST-4. Despite being isolated from five continents, Cfv and Cfvi genomes clustered closely, forming distinct branches at the biovar level; however, six Cfv genomes were located within Cfvi clades, suggesting a shared evolutionary lineage. In contrast, C. fetus subsp. testudinum (Cft) genomes, exhibiting 20 distinct STs, formed distinct clades from Cfv, Cfvi, and C. fetus subsp. fetus (Cff). While Cfv genomes from North America and Cfvi genomes from South America formed distinct geographic clusters, Cff genomes displayed no clear geographical patterns, with branches containing strains from multiple continents, indicating a globally dispersed distribution. Pangenomic analysis revealed pronounced clustering within Cft, characterized by unique gene presence/absence patterns. Five distinct AMR genes were detected, with tet(O) (n = 3) being the most common. Horizontal gene transfer analysis identified 140 genomic islands across 41 genomes, and virulence factor analysis revealed cheY as the sole conserved virulence gene across 35 genomes. ConclusionThese findings provide critical insights into the genomic diversity, zoonotic potential, and global distribution of C. fetus, emphasizing the need for integrated genomic and epidemiological strategies to assess its impact on human and animal health.

genomics↗

Large pan-cancer cell screen coupled to (phospho-) proteomics underscores high-dose vitamin C as a potent anti-cancer agent

Increasing preclinical and clinical evidence has positioned high-dose vitamin C as a promising anti-cancer treatment that merits more clinical attention. Multiple cytotoxicity mechanisms have been described, including pro-oxidant effects. To contribute to the preclinical understanding of the broad pan-cancer effects of high-dose vitamin C in a global manner, we determined the IC50 of a large panel of cancer cell lines (n=51) representing 7 solid tumour types and generated proteome data. The majority of cell lines were highly sensitive (IC50 range 0.036-10mM, mean 1.7 {+/-} 0.4 mM), well below a clinically achievable dose. The proteome data (>5000 proteins per sample), showed that high sensitivity is associated with proliferation, as indicated by functional enrichment of cell cycle, RNA splicing and chromatin organization, while lower sensitivity is linked to extracellular vesicles, glycolysis, fatty acid metabolism and mitochondria. Moreover, (phospho-)proteome analysis of on-treatment vitamin C effects on four pancreatic ductal adenocarcinoma (PDAC) cells dosed at a range of IC50 values (Hs766 T, 2 mM; Capan-2, 0.6 mM; PANC-1, 0.14 mM and Suit-2, 0.1 mM) revealed, next to cell line specific effects, down-modulation of AKT-MTOR signalling and immune suppressive signalling, while IFN- response was enhanced upon vitamin C. Altogether, our comprehensive pharmacological and (phospho-)proteome analysis is the first to assess cancer vulnerabilities and effects of vitamin C on a large cancer cell line panel and underscores the potential of high-dose vitamin C as an anti-cancer agent.

cancer biology↗