ABSTRACT: Chemical Proportionality Experiment of B.subtilis with antibiotics & pesticides such as Sulfamethoxazole, sulfadimethoxine and asulam to look for potential biotransformation
Project description:Chemical Proportionality Experiment of B.subtilis with antibiotics & pesticides such as Sulfamethoxazole, sulfadimethoxine and asulam to look for potential biotransformation
Project description:Chemical Proportionality Experiment of B.subtilis and E.coli added with pooled antibiotics (Sulfamethoxazole, sulfadimethoxine, cyproconazole and asulam) to look for potential biotransformation.
Project description:Chemical Proportionality Experiment of B.subtilis and E.coli added with pooled antibiotics (Sulfamethoxazole, sulfadimethoxine, cyproconazole and asulam) to look for potential biotransformation.
Project description:RNA sequencing was performed on E. coli K12 MG1655 on three media (M9, CA-MHB, R10LB) treated with four antibiotics (Ciprofloxacin, Trimethoprim-sulfamethoxazole, Ceftriaxone, Meropenem) at their media-specific MIC90s
Project description:To assay every gene in the E. coli genome to identify those that contribute to increased or decreased susceptibility to the antibiotics trimethoprim and sulfamethoxazole. This will help to define more accurately those bacterial cell mechanisms that contribute to these phenomena and provide information that will contribute to the development of new antibiotics, or compounds or known antibiotics that synergise with those already in clinical use. Thus, this set of experiments confirmed that AZT, widely known for its antiviral activity, acts synergistically with trimehoprim.
Project description:Humans are exposed to numerous xenobiotics, a majority of which are in the form of pharmaceuticals. Apart from human enzymes, recent studies have indicated the role of the gut bacterial community (microbiome) in metabolizing xenobiotics. However, little is known about the contribution of the plethora of gut microbiome in xenobiotic metabolism. The present study reports the results of analyses on xenobiotic metabolizing enzymes in various human gut microbiomes. A total of 397 available gut metagenomes from individuals of varying age groups from 8 nationalities were analyzed. Based on the diversities and abundances of the xenobiotic metabolizing enzymes, various bacterial taxa were classified into three groups, namely, least versatile, intermediately versatile and highly versatile xenobiotic metabolizers. Most interestingly, specific relationships were observed between the overall drug consumption profile and the abundance and diversity of the xenobiotic metabolizing repertoire in various geographies. The obtained differential abundance patterns of xenobiotic metabolizing enzymes and bacterial genera harboring them, suggest their links to pharmacokinetic variations among individuals. Additional analyses of a few well studied classes of drug modifying enzymes (DMEs) also indicate geographic as well as age specific trends.
Project description:Xenobiotics are ubiquitous in the environment and modified abundantly in the human body by phase I and II metabolism. Liquid chromatography coupled to high resolution mass spectrometry is a powerful tool to investigate these biotransformation products. Here, we present a workflow based on stable isotope-assisted metabolomics and the bioinformatics tool MetExtract II for deciphering all measureable xenobiotic metabolites produced by human cells in vitro in an untargeted manner. The value of this workflow is demonstrated by the detailed investigation of the metabolism of deoxynivalenol (DON), an abundant food contaminant, in two cell models (HepG2, HT29). Detected known metabolites included DON-3-sulfate, DON-10-sulfonate, and DON-10-glutathione as well as DON-cysteine. Conjugation with amino acids and antibiotics was observed and confirmed for the first time. The approach allows for the generic and untargeted elucidation of human xenobiotic products in tissue culture. It may be easily applied to other fields of research including drug metabolism, personalized medicine and systems biology and serves to better understand the relevance of in vitro experiments.
Project description:Animals have developed extensive mechanisms of response to xenobiotic chemical attacks. Although recent genome surveys have suggested a broad conservation of the chemical defensome across metazoans, global gene expression responses to xenobiotics are not known in most invertebrates. Here, using high density tiling arrays with over 2 million probes, we explored genome-wide gene expression in the tunicate Oikopleura dioica in response to two model xenobiotic chemicals – the carcinogenic polycyclic aromatic hydrocarbon benzo[a]pyrene (BaP) the pharmaceutical compound Clofibrate (Clo). The genotoxic compound BaP induced xenobiotic biotransformation and oxidative stress responsive genes, as in vertebrates. Notable exceptions were genes of the aryl hydrocarbon receptor (AhR) signaling pathway. Clo also affected the expression of many biotransformation genes and markedly repressed genes involved in energy metabolism and muscle contraction pathways. Oikopleura appears to have basic defensome toolkit consisting of phase I, phase II and phase III biotransformation genes.
Project description:The response of antibiotic adapted resistant mutants of B. cenocepacia J2315 to antibiotic stress was investigated using expression profiling of three biological replicates and comparing the profiles to the J2315 parent control grown without antibiotics.<br>A reference design was used with Cy3 labeled genomic DNA of B. cenocepacia J2315 as common reference. Three test conditions with three biological replicates each were compared to three replicates of the control condition.<br>Test conditions: J2315-A grown in the presence of 250 ug per ml amikacin, J2315-M grown in the presence of 8 ug per ml meropenem and J2315-T grown in the presence of 60 ug per ml trimethoprim and 300 ug per ml sulfamethoxazole.<br>Control condition: J2315 parent strain grown without antibiotics.
Project description:Non-alcoholic fatty liver disease (NAFLD), the hepatic manifestation of the metabolic syndrome, is a complex multifactorial disease characterized by metabolic deregulations that include accumulation of lipids in the liver, lipotoxicity, and insulin resistance. The progression of NAFLD to non-alcoholic steatohepatitis and cirrhosis, and ultimately to carcinomas, is governed by interplay of pro-inflammatory pathways, oxidative stress, as well as fibrogenic and apoptotic cues. As the liver is the major organ of biotransformation, deregulations in hepatic signaling pathways have effects on both, xenobiotic and endobiotic metabolism. Several major nuclear receptors involved in the transcription and regulation of phase I and II drug metabolizing enzymes and transporters also have endobiotic ligands including several lipids. Hence, hepatic lipid accumulation in steatosis and NAFLD, which leads to deregulated activation patterns of nuclear receptors, may result in altered drug metabolism capacity in NAFLD patients. On the other hand, genetic and association studies have indicated that a malfunction in drug metabolism can affect the prevalence and severity of NAFLD. This review focuses on the complex interplay between NAFLD pathogenesis and drug metabolism. A better understanding of these relationships is a prerequisite for developing improved drug dosing algorithms for the pharmacotherapy of patients with different stages of NAFLD.