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Cook, G.

Publications and source records attributed to Cook, G..

2 recordsLinked to original sources

Appearance of synthetic vector-associated antibiotic resistance genes in next-generation sequences

SynopsisO_ST_ABSBackgroundC_ST_ABSNext-generation sequencing methods have broad application in addressing increasing antibiotic resistance, with identification of antibiotic resistance genes (ARGs) having direct clinical relevance.\n\nObjectivesHere, we describe the appearance of synthetic vector-associated ARGs in major public next-generation sequence data sets and assemblies, including in environmental samples and high priority pathogenic microorganisms.\n\nMethodsA search of selected databases - the National Centre for Biotechnology Information (NCBI) nucleotide collection, NCBI whole genome shotgun sequence contigs and literature-associated European Nucleotide Archive (ENA) datasets, was carried out using sequences characteristic of pUC-family synthetic vectors as a query in BLASTn. Identified hits were confirmed as being of synthetic origin, and further explored through alignment and comparison to primary read sets.\n\nResultsSynthetic vectors are attributed to a range of organisms in each of the NCBI databases searched, including examples belonging to each Kingdom of life. These synthetic vectors are associated with various ARGs, primarily those encoding resistance to beta-lactam antibiotics and aminoglycosides. Synthetic vector associated ARGs are also observed in multiple environmental meta-transcriptome datasets, as shown through analysis of associated ENA primary reads, and are proposed to have led to incorrect statements being made in the literature on the abundance of ARGs.\n\nConclusionsAppearance of synthetic vector-associated ARGs can confound the study of antimicrobial resistance in varied settings, and may have clinical implications in the nearfuture.

microbiology

A novel mitochondrial enriched antioxidant protects neurons against acute oxidative stress

Excessive reactive oxygen species (ROS) can damage proteins, lipids, and DNA, which result in cell damage and death. The outcomes can be acute, as seen in stroke, or more chronic as observed in age-related diseases such as Parkinsons disease. Here we investigate the antioxidant ability of a novel synthetic flavonoid, Proxison (7-decyl-3-hydroxy-2-(3,4,5-trihydroxyphenyl)-4-chromenone), using a range of in vitro and in vivo approaches. We show that, while it has radical scavenging ability on par with other flavonoids in a cell-free system, Proxison is orders of magnitude more potent than natural flavonoids at protecting neural cells against oxidative stress and is capable of rescuing damaged cells. The unique combination of a lipophilic hydrocarbon tail with a modified polyphenolic head group promotes efficient cellular uptake and mitochondrial localisation of Proxison. Importantly, in vivo administration of Proxison demonstrated effective and well tolerated neuroprotection against oxidative stress in a zebrafish model of dopaminergic neuronal loss.

cell biology