Genome-wide analysis of fitness-factors in uropathogenic during growth in laboratory media and during urinary tract infections.

Uropathogenic (UPEC) UTI89 is a well-characterized strain, which has mainly been used to study UPEC virulence during urinary tract infection (UTI). However, little is known on UTI89 key fitness-factors during growth in lab media and during UTI. Here, we used a transposon-insertion-sequencing approach (TraDIS) to reveal the UTI89 essential-genes for growth and fitness-gene-sets for growth in Luria broth (LB) and EZ-MOPS medium without glucose, as well as for human bacteriuria and mouse cystitis.

The Effect of Colistin Treatment on the Selection of Colistin-Resistant in Weaner Pigs.

The treatment of diarrhea in the postweaning period is a common reason for the use of antimicrobials in pig production, and is the single most important causative agent for this condition. Colistin has recently been classified as a critically important antimicrobial for human health, as it is a last-resort drug against certain multi-drug-resistant Gram-negative bacteria. Therefore, the use of colistin has been significantly reduced in some countries, including Denmark.

Abundance of Mobilized Colistin Resistance Gene () in Commensal from Diverse Sources.

Antimicrobial resistance (AMR) spreads not only by pathogenic but also by commensal bacteria, and the latter can become a reservoir for resistance genes. This study was aimed to investigate the AMR patterns along with the presence of mobilized colistin resistance () genes in commensal circulating in chickens, farm environments, street foods, and human patients. By a cross-sectional survey, isolates obtained from 530 samples were tested for their AMR profiles against 9 antimicrobials.

High prevalence of mcr-1-encoded colistin resistance in commensal Escherichia coli from broiler chicken in Bangladesh.

Colistin is a last-resort antimicrobial used for the treatment of human infections caused by multidrug-resistant Gram-negative bacteria. However, colistin is still widely used in intensive poultry production in Bangladesh. We aimed to investigate the dynamics and genetic diversity of colistin-resistant commensal Escherichia coli from broiler chickens.

Epidemiology of Serovar Dublin in Cattle and Humans in Denmark, 1996 to 2016: a Retrospective Whole-Genome-Based Study.

serovar Dublin is a cattle-adapted serovar causing both intestinal and systemic infection in its bovine host, and it is also a serious threat to human health. The present study aimed to determine the population structure of Dublin isolates obtained from Danish cattle herds and to investigate how cattle isolates relate to Danish human isolates, as well as to non-Danish human and bovine isolates. Phylogenetic analysis of 197 Danish cattle isolates from 1996 to 2016 identified three major clades corresponding to distinct geographical regions of cattle herds.

The SPI-19 encoded type-six secretion-systems (T6SS) of Salmonella enterica serovars Gallinarum and Dublin play different roles during infection.

Salmonella Pathogenicity Islands 19 (SPI19) encodes a type VI secretion system (T6SS). SPI19 is only present in few serovars of S. enterica, including the host-adapted serovar S.

Targeted Resequencing of the Coding Sequence of 38 Genes Near Breast Cancer GWAS Loci in a Large Case-Control Study.

Background: Genes regulated by breast cancer risk alleles identified through genome-wide association studies (GWAS) may harbor rare coding risk alleles.

Methods: We sequenced the coding regions for 38 genes within 500 kb of 38 lead GWAS SNPs in 13,538 breast cancer cases and 5,518 controls.

Results: Truncating variants in these genes were rare, and were not associated with breast cancer risk.

The impact of inactivation of the purine biosynthesis genes, purN and purT, on growth and virulence in uropathogenic E. coli.

De novo synthesis of purines has been suggested to be an important factor for the pathogenesis of uropathogenic E. coli (UPEC). We analyzed the role of the redundant purine biosynthesis genes purN and purT, responsible for the third step in the purine biosynthesis, during UPEC infection.

The Use of a Combined Bioinformatics Approach to Locate Antibiotic Resistance Genes on Plasmids From Whole Genome Sequences of Serovars From Humans in Ghana.

In the current study, we identified plasmids carrying antimicrobial resistance genes in draft whole genome sequences of 16 selected isolates representing six different serovars from humans in Ghana. The plasmids and the location of resistance genes in the genomes were predicted using a combination of PlasmidFinder, ResFinder, plasmidSPAdes and BLAST genomic analysis tools. Subsequently, S1-PFGE was employed for analysis of plasmid profiles.

Publisher Correction: Evidence that breast cancer risk at the 2q35 locus is mediated through IGFBP5 regulation.

This corrects the article DOI: 10.1038/ncomms5999.

Genetic overlap between endometriosis and endometrial cancer: evidence from cross-disease genetic correlation and GWAS meta-analyses.

Epidemiological, biological, and molecular data suggest links between endometriosis and endometrial cancer, with recent epidemiological studies providing evidence for an association between a previous diagnosis of endometriosis and risk of endometrial cancer. We used genetic data as an alternative approach to investigate shared biological etiology of these two diseases. Genetic correlation analysis of summary level statistics from genomewide association studies (GWAS) using LD Score regression revealed moderate but significant genetic correlation (r = 0.

The membrane transporter PotE is required for virulence in avian pathogenic Escherichia coli (APEC).

Over the last few years, polyamines have been described as key-signal of virulence in pathogenic bacteria. In the current study, we investigated whether the knockout of genes related to polyamine biosynthesis and putrescine transport affected the virulence of an avian pathogenic E. coli (APEC) strain.

Identification of ten variants associated with risk of estrogen-receptor-negative breast cancer.

Most common breast cancer susceptibility variants have been identified through genome-wide association studies (GWAS) of predominantly estrogen receptor (ER)-positive disease. We conducted a GWAS using 21,468 ER-negative cases and 100,594 controls combined with 18,908 BRCA1 mutation carriers (9,414 with breast cancer), all of European origin. We identified independent associations at P < 5 × 10 with ten variants at nine new loci.

Rare, protein-truncating variants in , and , but not , are associated with increased breast cancer risks.

Background: Breast cancer (BC) is the most common malignancy in women and has a major heritable component. The risks associated with most rare susceptibility variants are not well estimated. To better characterise the contribution of variants in , , and , we sequenced their coding regions in 13 087 BC cases and 5488 controls from East Anglia, UK.

The genetic diversity of commensal Escherichia coli strains isolated from non-antimicrobial treated pigs varies according to age group.

This is the first report on the genetic diversity of commensal E. coli from pigs reared in an antibiotic free production system and belonging to different age groups. The study investigated the genetic diversity and relationship of 900 randomly collected commensal E.

Effect of Tetracycline Dose and Treatment Mode on Selection of Resistant Coliform Bacteria in Nursery Pigs.

This study describes the results of a randomized clinical trial investigating the effect of oxytetracycline treatment dose and mode of administration on the selection of antibiotic-resistant coliform bacteria in fecal samples from nursery pigs. Nursery pigs (pigs of 4 to 7 weeks of age) in five pig herds were treated with oxytetracycline for -induced diarrhea. Each group was randomly allocated to one of five treatment groups: oral flock treatment with a (i) high (20 mg/kg of body weight), (ii) medium (10 mg/kg), or (iii) low (5 mg/kg) dose, (iv) oral pen-wise (small-group) treatment (10 mg/kg), and (v) individual intramuscular injection treatment (10 mg/kg).

Genotype variation and genetic relationship among Escherichia coli from nursery pigs located in different pens in the same farm.

Background: So far, little is known about the genetic diversity and relatedness among Escherichia coli (E. coli) populations in the gut of swine. Information on this is required to improve modeling studies on antimicrobial resistance aiming to fight its occurrence and development.

Genetic Risk Score Mendelian Randomization Shows that Obesity Measured as Body Mass Index, but not Waist:Hip Ratio, Is Causal for Endometrial Cancer.

Background: The strongest known risk factor for endometrial cancer is obesity. To determine whether SNPs associated with increased body mass index (BMI) or waist-hip ratio (WHR) are associated with endometrial cancer risk, independent of measured BMI, we investigated relationships between 77 BMI and 47 WHR SNPs and endometrial cancer in 6,609 cases and 37,926 country-matched controls.

Methods: Logistic regression analysis and fixed effects meta-analysis were used to test for associations between endometrial cancer risk and (i) individual BMI or WHR SNPs, (ii) a combined weighted genetic risk score (wGRS) for BMI or WHR.

Meta-analysis of Genome Wide Association Studies Identifies Genetic Markers of Late Toxicity Following Radiotherapy for Prostate Cancer.

Nearly 50% of cancer patients undergo radiotherapy. Late radiotherapy toxicity affects quality-of-life in long-term cancer survivors and risk of side-effects in a minority limits doses prescribed to the majority of patients. Development of a test predicting risk of toxicity could benefit many cancer patients.

Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus.

Background: Multiple recent genome-wide association studies (GWAS) have identified a single nucleotide polymorphism (SNP), rs10771399, at 12p11 that is associated with breast cancer risk.

Method: We performed a fine-scale mapping study of a 700 kb region including 441 genotyped and more than 1300 imputed genetic variants in 48,155 cases and 43,612 controls of European descent, 6269 cases and 6624 controls of East Asian descent and 1116 cases and 932 controls of African descent in the Breast Cancer Association Consortium (BCAC; http://bcac.ccge.

Five endometrial cancer risk loci identified through genome-wide association analysis.

We conducted a meta-analysis of three endometrial cancer genome-wide association studies (GWAS) and two follow-up phases totaling 7,737 endometrial cancer cases and 37,144 controls of European ancestry. Genome-wide imputation and meta-analysis identified five new risk loci of genome-wide significance at likely regulatory regions on chromosomes 13q22.1 (rs11841589, near KLF5), 6q22.

No evidence that protein truncating variants in BRIP1 are associated with breast cancer risk: implications for gene panel testing.

Background: BRCA1 interacting protein C-terminal helicase 1 (BRIP1) is one of the Fanconi Anaemia Complementation (FANC) group family of DNA repair proteins. Biallelic mutations in BRIP1 are responsible for FANC group J, and previous studies have also suggested that rare protein truncating variants in BRIP1 are associated with an increased risk of breast cancer. These studies have led to inclusion of BRIP1 on targeted sequencing panels for breast cancer risk prediction.

Meta-analysis of genome-wide association studies identifies common susceptibility polymorphisms for colorectal and endometrial cancer near SH2B3 and TSHZ1.

High-risk mutations in several genes predispose to both colorectal cancer (CRC) and endometrial cancer (EC). We therefore hypothesised that some lower-risk genetic variants might also predispose to both CRC and EC. Using CRC and EC genome-wide association series, totalling 13,265 cancer cases and 40,245 controls, we found that the protective allele [G] at one previously-identified CRC polymorphism, rs2736100 near TERT, was associated with EC risk (odds ratio (OR) = 1.

Comprehensive genetic assessment of the ESR1 locus identifies a risk region for endometrial cancer.

Excessive exposure to estrogen is a well-established risk factor for endometrial cancer (EC), particularly for cancers of endometrioid histology. The physiological function of estrogen is primarily mediated by estrogen receptor alpha, encoded by ESR1. Consequently, several studies have investigated whether variation at the ESR1 locus is associated with risk of EC, with conflicting results.

Height and Breast Cancer Risk: Evidence From Prospective Studies and Mendelian Randomization.

Background: Epidemiological studies have linked adult height with breast cancer risk in women. However, the magnitude of the association, particularly by subtypes of breast cancer, has not been established. Furthermore, the mechanisms of the association remain unclear.