Complete nucleotide sequence of pVQS1 containing a quinolone resistance determinant from Salmonella enterica serovar Virchow associated with foreign travel

Nalidixic acid-resistant Salmonella enterica serovars Kentucky (n5) and Virchow (n6) cultured from individuals were investigated for the presence of plasmid-mediated quinolone resistance (PMQR) determinants.

PMQR markers and mutations within the quinolone resistance-determining regions of the target genes were investigated by PCR followed by DNA sequencing. Conjugation, plasmid profiling and targeted PCR were performed to demonstrate the transferability of the qnrS1 gene. Subsequently, a plasmid was identified that carried a quinolone resistance marker and this was completely sequenced.

A Salmonella Virchow isolate carried a qnrS1 gene associated with an IncN incompatibility group conjugative plasmid of 40995 bp, which was designated pVQS1. The latter conferred resistance to ampicillin and nalidixic acid and showed sequence similarity in its core region to plasmid R46, whilst the resistance-encoding region was similar to pAH0376 from Shigella flexneri and pINF5 from Salmonella Infantis and contained an IS26 remnant, a complete Tn3 structure, a truncated IS2 element and a qnrS1 marker, followed by IS26. In contrast to pINF5, IS26 was identified immediately downstream of the qnrS1 gene.

This is the first known report of a qnrS1 gene in Salmonella spp. in Switzerland. Analysis of the complete nucleotide sequence of the qnrS1-containing plasmid showed a novel arrangement of this antibiotic resistance-encoding region.

New genetic loci link adipose and insulin biology to body fat distribution

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.

Genetic studies of body mass index yield new insights for obesity biology

Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.