ABSTRACT: Whole genome sequencing analysis of environmental vancomycin resistant Enterococcus spp. isolated from hospital wastewater to water resources
Project description:Whole genome sequencing analysis of environmental vancomycin resistant Enterococcus spp. isolated from hospital wastewater to water resources
Project description:Traditional vaccines are difficult to deploy against the diverse antibiotic-resistant, nosocomial pathogens that cause Hospital Acquired Infections (HAIs). We developed a unique, protein-free vaccine to present antibiotic-resistant HAIs. This vaccine protected mice from invasive infections caused by methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecalis, multidrug resistant Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa, Rhizopus delemar, and Candida albicans. Protection persisted even in neutropenic mice infected with A. baumannii or R. delemar. Protection was already apparent after 24 hours and lasted for up to 21 days after a single dose, with a second dose restoring efficacy. Protection persisted without lymphocytes but was abrogated with macrophages depletion. This vaccine induced trained immunity by altering the macrophage epigenetic landscape and the inflammatory response to infection.
Project description:In this study, we exposed Caenorhabditis elegans wild types N2 to water collected from six sources in the Dutch village Sneek. The sources were: wastewater from a hospital, a community (80 households), a nursing home, influent into the local municipal wastewater treatment plant, effluent of the wastewater treatment plant, and surface water samples. The goal of the experiment was to determine if C. elegans can be used to identify pollutants in the water by transcriptional profiling. Age synchronized worms at developmental L4 larval stage were exposed to treatment for 24 hours. After flash freezing the samples, RNA was isolated, labeled and hybridized on oligo microarray (Agilent) slides.
Project description:This study aims to determine the global gene expression in vancomycin resistant Enterococcus faecium (VRE) in response to a novel essential oil-vancomycin combination, and the individual components (vancomycin, carvacrol and cuminaldehyde) to help determine the mechanism of action of this antimicrobial formulation. This formulation increases the susceptibility of VRE to vancomycin and the array provides data on the synergistic mechanism of action. Five conditions (1. Control; 2. Carvacrol, 1.98 mM; 3. Cuminaldehyde, 4.20 mM; 4. Vancomycin, 0.031 mg/l; 5. Combination, 1.98 mM Carvacrol, 4.2 mM Cuminaldehyde, 0.031 mg/l vancomycin) all with 1% DMSO were tested in triplicate with a 60 minute exposure time before extraction.
Project description:Preliminary analysis on extracts (pellets and supernatant) of vancomycin-resistant Enterococcus faecium strains cultured in BHI media. Untargeted LC-MS/MS acquisition performed in positive ion mode.
Project description:The rise of antibiotic resistance and decline of antibiotic discovery urgently calls for novel mechanistic understanding of pharmacological and evolutionary interactions between antibiotics and multidrug resistant bacteria to revitalize existing antibiotics. The evolutionary cross-resistance to antibiotics has received intensive attention previously. Nevertheless, whether and how bacteria develop negative responses, under the selective pressure of antibiotics by inverting the evolutionary trajectory remains unclear. Here we found an instance of collateral sensitivity, in which clinical vancomycin-resistant Enterococcus faecium (VREfm) pathogens exhibit dramatic and specific susceptibility to pleuromutilin antibiotics, decreased minimal inhibitory concentrations (MICs) from 128 µg/mL to 0.03 µg/mL. The unique trade-off between vancomycin and pleuromutilins is mediated by the epistasis between the van gene cluster and msrC encoding an ABC-F protein protecting bacterial ribosomes. We validated the efficacy of pleuromutilins in vivo through reducing colonization and promoting microbiota restoration. Our findings provide an alternative approach to inverting the selective advantage and reversing the route of vancomycin resistance evolution, and to treat VREfm associated infections.
