Cobalt complexes modulate plasmid conjugation in Escherichia coli and Klebsiella pneumoniae.

Antimicrobial resistance genes (ARG), such as extended-spectrum β-lactamase (ESBL) and carbapenemase genes, are commonly carried on plasmids. Plasmids can transmit between bacteria, disseminate globally, and cause clinically important resistance. Therefore, targeting plasmids could reduce ARG prevalence, and restore the efficacy of existing antibiotics.

Non-antibiotic compounds associated with humans and the environment can promote horizontal transfer of antimicrobial resistance genes.

Horizontal gene transfer plays a key role in the global dissemination of antimicrobial resistance (AMR). AMR genes are often carried on self-transmissible plasmids, which are shared amongst bacteria primarily by conjugation. Antibiotic use has been a well-established driver of the emergence and spread of AMR.

Growth in a biofilm promotes conjugation of a -bearing plasmid between strains.

Antimicrobial resistance (AMR) is a growing problem, especially in Gram-negative Enterobacteriaceae such as . Horizontal transfer of conjugative plasmids contributes to AMR gene dissemination. Bacteria such as commonly exist in biofilms, yet most studies focus on planktonic cultures.

In situ, in vivo, and in vitro approaches for studying AMR plasmid conjugation in the gut microbiome.

Antimicrobial resistance (AMR) is a global threat, with evolution and spread of resistance to frontline antibiotics outpacing the development of novel treatments. The spread of AMR is perpetuated by transfer of antimicrobial resistance genes (ARGs) between bacteria, notably those encoded by conjugative plasmids. The human gut microbiome is a known 'melting pot' for plasmid conjugation, with ARG transfer in this environment widely documented.

EnvR is a potent repressor of acrAB transcription in Salmonella.

Background: Resistance nodulation division (RND) family efflux pumps, including the major pump AcrAB-TolC, are important mediators of intrinsic and evolved antibiotic resistance. Expression of these pumps is carefully controlled by a network of regulators that respond to different environmental cues. EnvR is a TetR family transcriptional regulator encoded upstream of the RND efflux pump acrEF.

Abiraterone acetate plus prednisolone for metastatic patients starting hormone therapy: 5-year follow-up results from the STAMPEDE randomised trial (NCT00268476).

Abiraterone acetate plus prednisolone (AAP) previously demonstrated improved survival in STAMPEDE, a multiarm, multistage platform trial in men starting long-term hormone therapy for prostate cancer. This long-term analysis in metastatic patients was planned for 3 years after the first results. Standard-of-care (SOC) was androgen deprivation therapy.

Abiraterone acetate and prednisolone with or without enzalutamide for high-risk non-metastatic prostate cancer: a meta-analysis of primary results from two randomised controlled phase 3 trials of the STAMPEDE platform protocol.

Background: Men with high-risk non-metastatic prostate cancer are treated with androgen-deprivation therapy (ADT) for 3 years, often combined with radiotherapy. We analysed new data from two randomised controlled phase 3 trials done in a multiarm, multistage platform protocol to assess the efficacy of adding abiraterone and prednisolone alone or with enzalutamide to ADT in this patient population.

Methods: These open-label, phase 3 trials were done at 113 sites in the UK and Switzerland.

HIV Drugs Inhibit Transfer of Plasmids Carrying Extended-Spectrum β-Lactamase and Carbapenemase Genes.

Antimicrobial-resistant (AMR) infections pose a serious risk to human and animal health. A major factor contributing to this global crisis is the sharing of resistance genes between different bacteria via plasmids. The WHO lists , such as and , producing extended-spectrum β-lactamases (ESBL) and carbapenemases as "critical" priorities for new drug development.

Bacterial flagellin promotes viral entry via an NF-kB and Toll Like Receptor 5 dependent pathway.

Viruses and bacteria colonize hosts by invading epithelial barriers. Recent studies have shown that interactions between the microbiota, pathogens and the host can potentiate infection through poorly understood mechanisms. Here, we investigated whether diverse bacterial species could modulate virus internalization into host cells, often a rate-limiting step in establishing infections.

Strategies to combat antimicrobial resistance: anti-plasmid and plasmid curing.

Antimicrobial resistance (AMR) is a global problem hindering treatment of bacterial infections, rendering many aspects of modern medicine less effective. AMR genes (ARGs) are frequently located on plasmids, which are self-replicating elements of DNA. They are often transmissible between bacteria, and some have spread globally.

Clinically Relevant Plasmid-Host Interactions Indicate that Transcriptional and Not Genomic Modifications Ameliorate Fitness Costs of Carbapenemase-Carrying Plasmids.

The rapid dissemination of antimicrobial resistance (AMR) around the globe is largely due to mobile genetic elements, such as plasmids. They confer resistance to critically important drugs, including extended-spectrum beta-lactams, carbapenems, and colistin. Large, complex resistance plasmids have evolved alongside their host bacteria.

Quinolone-resistant gyrase mutants demonstrate decreased susceptibility to triclosan.

Objectives: Cross-resistance between antibiotics and biocides is a potentially important driver of MDR. A relationship between susceptibility of Salmonella to quinolones and triclosan has been observed. This study aimed to: (i) investigate the mechanism underpinning this; (ii) determine whether the phenotype is conserved in Escherichia coli; and (iii) evaluate the potential for triclosan to select for quinolone resistance.

Beyond Antimicrobial Resistance: Evidence for a Distinct Role of the AcrD Efflux Pump in Salmonella Biology.

Unlabelled: For over 20 years, bacterial multidrug resistance (MDR) efflux pumps have been studied because of their impact on resistance to antimicrobials. However, critical questions remain, including why produce efflux pumps under non-antimicrobial treatment conditions, and why have multiple pumps if their only purpose is antimicrobial efflux? Salmonella spp. possess five efflux pump families, including the resistance-nodulation-division (RND) efflux pumps.

Ciprofloxacin and ceftriaxone alter cytokine responses, but not Toll-like receptors, to Salmonella infection in vitro.

Objectives: Antibiotics that enhance host natural defences to infection offer an alternative approach to treating infections. However, mechanisms underlying such processes are poorly understood. The aim of this study was to investigate the effects of clinically relevant concentrations of two antibiotics on bacterial interactions with murine macrophages.

15-Deoxy-Δ12,14-prostaglandin J2 inhibits macrophage colonization by Salmonella enterica serovar Typhimurium.

15-deoxy-Δ(12,14)-prostaglandin J2 (15d-PGJ2) is an anti-inflammatory downstream product of the cyclooxygenase enzymes. It has been implicated to play a protective role in a variety of inflammatory mediated diseases, including rheumatoid arthritis, neural damage, and myocardial infarctions. Here we show that 15d-PGJ2 also plays a role in Salmonella infection.

A comprehensive study of the contribution of Salmonella enterica serovar Typhimurium SPI2 effectors to bacterial colonization, survival, and replication in typhoid fever, macrophage, and epithelial cell infection models.

Salmonella enterica serovars are Gram-negative bacterial pathogens responsible for human diseases including gastroenteritis and typhoid fever. After ingestion, Salmonella cross the intestinal epithelial barrier, where they are phagocytosed by macrophages and dendritic cells, which then enables their spread to systemic sites during cases of typhoid fever. Salmonella use two type 3 secretion systems encoded by Salmonella pathogenicity islands (SPI) 1 and 2 to inject virulence proteins into host cells to modify cellular functions.

Impact of salmonella infection on host hormone metabolism revealed by metabolomics.

The interplay between pathogens and their hosts has been studied for decades using targeted approaches, such as the analysis of mutants and host immunological responses. Although much has been learned from such studies, they focus on individual pathways and fail to reveal the global effects of infection on the host. To alleviate this issue, high-throughput methods, such as transcriptomics and proteomics, have been used to study host-pathogen interactions.

The prognostic value of hemoglobin in patients with anal cancer treated with chemoradiotherapy.

Purpose: This study aimed to evaluate the impact of hemoglobin level on clinical outcome (local response, progression-free survival, and overall survival) in patients with carcinoma of the anal canal treated with definitive chemoradiotherapy.

Methods: This is a retrospective study of patients with anal cancer treated between 1992 and 2005 with definitive chemoradiotherapy at Tom Baker Cancer Centre. Patient treatment, laboratory, and outcome data were extracted from the chart.

Inhibition of Salmonella host cell invasion by dimethyl sulfide.

We show that dimethyl sulfoxide (DMSO) inhibits Salmonella hilA expression and that this inhibition is stronger under anaerobiosis. Because DMSO can be reduced to dimethyl sulfide (DMS) during anaerobic growth, we hypothesized that DMS was responsible for hilA inhibition. Indeed, DMS strongly inhibited the expression of hilA and multiple Salmonella pathogenicity island 1 (SPI-1)-associated genes as well as the invasion of cultured epithelial cells.

Quorum sensing in bacterial virulence.

Bacteria communicate through the production of diffusible signal molecules termed autoinducers. The molecules are produced at basal levels and accumulate during growth. Once a critical concentration has been reached, autoinducers can activate or repress a number of target genes.