Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.1.3 (ATPase)
 65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Resistance to bile is a prerequisite property of the gastrointestinal bacterial flora. Bile acids are powerful detergents, and resistance to sodium dodecyl sulfate (SDS) has therefore often been considered relevant to studies of bile resistance. We have studied the effects of bovine bile (BB) and SDS on Enterococcus faecalis V583 by traditional growth studies and microarrays. Transcriptional responses were studied by time course experiments. In the presence of BB (V583-BB) or SDS (V583-SDS), 308 and 209 genes were identified as differentially expressed at one or more time points, respectively. In V583 treated with both BB and SDS (V583-BB-SDS), 254 genes showed differential expression. Detergents exert their toxic effects primarily on the microbial membrane. The enrichment of differentially transcribed genes that encode proteins with membrane-associated functions and/or locations indicates a major impact of all three treatments on the integrity and functionality of the cell membrane. Two gene clusters involved in fatty acid biosynthesis were repressed in V583-BB and V583-BB-SDS and partly induced in V583-SDS. Furthermore, two EmrB/QacA family drug resistance transporters and a vacuolar-type ATPase were induced in V583-BB and V583-BB-SDS. None of the putative bile salt hydrolase homologs in V583 showed differential expression during the bile treatments. The transcriptional profile of V583-BB-SDS was qualitatively more similar to the response in V583-BB than to that in V583-SDS, suggesting that the presence of bile suppresses the effects of SDS in V583-BB-SDS. The overall results presented here indicate that different mechanisms are involved in detergent resistance in E. faecalis.
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PMID:Transcriptional responses of Enterococcus faecalis V583 to bovine bile and sodium dodecyl sulfate. 1766 Mar 10

The present investigation was aimed at studying the relative expression of atpD (a key part of F1F0-ATPase operon), bsh (bile salt hydrolase), mub (mucus-binding protein) and MUC2 (mucin) genes in mouse model for establishing the in vivo functional efficacy of Lactobacillus plantarum Lp91 (MTCC5690) by reverse transcription-quantitative PCR (RT-qPCR). The atpD gene was significantly up-regulated to 2.0, 2.4 and 3.2 folds in Lp91 after 15, 30 and 60 min transit in the stomach of mice. The maximal significant (P<0.00) level of relative bsh gene expression was recorded in Lp91 with 41.6 fold in comparison to only 5.0 fold in reference strain Lp5276 after seven days of mice feeding. Simultaneously, mub gene expression increased to 12.8 and 22.7 fold in both Lp91 and Lp5276, respectively. The expression level of MUC2 was at the level of 1.6 and 2.1 fold in the host colon on administration with Lp91 and Lp5276 feeding, respectively. Hence, the expression of atpD, bsh, mub, MUC2 could be considered as prospective and potential biomarkers for screening of novel probiotic lactobacillus strains for optimal functionality in the gut.
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PMID:Relative expression of bacterial and host specific genes associated with probiotic survival and viability in the mice gut fed with Lactobacillus plantarum Lp91. 2372 92

Pharmacokinetic research at the host-microbe interface has been primarily directed toward effects on drug metabolism, with fewer investigations considering the absorption process. We previously demonstrated that the transcriptional expression of genes encoding intestinal transporters involved in lipid translocation are altered in germ-free and conventionalized mice possessing distinct bile acid signatures. It was consequently hypothesized that microbial bile acid metabolism, which is the deconjugation and dehydroxylation of the bile acid steroid nucleus by gut bacteria, may impact upon drug transporter expression and/or activity and potentially alter drug disposition. Using a panel of three human intestinal cell lines (Caco-2, T84, and HT-29) that differ in basal transporter expression level, bile acid conjugation-, and hydroxylation-status was shown to influence the transcription of genes encoding several major influx and efflux transporter proteins. We further investigated if these effects on transporter mRNA would translate to altered drug disposition and activity. The results demonstrated that the conjugation and hydroxylation status of the bile acid steroid nucleus can influence the cellular response to multidrug resistance (MDR) substrates, a finding that did not directly correlate with directionality of gene or protein expression. In particular, we noted that the cytotoxicity of cyclosporine A was significantly augmented in the presence of the unconjugated bile acids deoxycholic acid (DCA) and chenodeoxycholic acid (CDCA) in P-gp positive cell lines, as compared to their taurine/glycine-conjugated counterparts, implicating P-gp in the molecular response. Overall this work identifies a novel mechanism by which gut microbial metabolites may influence drug accumulation and suggests a potential role for the microbial bile acid-deconjugating enzyme bile salt hydrolase (BSH) in ameliorating multidrug resistance through the generation of bile acid species with the capacity to access and inhibit P-gp ATPase. The physicochemical property of nonionization is suggested to underpin the preferential ability of unconjugated bile acids to attenuate the efflux of P-gp substrates and to sensitize tumorigenic cells to cytotoxic therapeutics in vitro. This work provides new impetus to investigate whether perturbation of the gut microbiota, and thereby the bile acid component of the intestinal metabolome, could alter drug pharmacokinetics in vivo. These findings may additionally contribute to the development of less toxic P-gp modulators, which could overcome MDR.
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PMID:Gut Microbiota-Mediated Bile Acid Transformations Alter the Cellular Response to Multidrug Resistant Transporter Substrates in Vitro: Focus on P-glycoprotein. 3038 19

In our previous studies, Lactobacillus plantarum Y44 showed antioxidant activity and favorable gastric and intestinal transit tolerance. In the current study, we investigated the physiological function of L. plantarum Y44 based on an analysis of its genotype and phenotype. The complete genome of L. plantarum Y44 contained a single circular chromosome of 3,255,555 bp, with a GC content of 44.6%, and a single circular plasmid of 51,167 bp, with a GC content of 38.8%. The L. plantarum Y44 genome contained 3,293 genes including 3,112 protein coding sequences, 16 rRNAs, 66 tRNAs, 4 small (s)RNAs, and 95 pseudo genes. Lactobacillus plantarum Y44 could metabolize 24 different carbohydrate sources. Nineteen complete phosphoenolpyruvate-dependent sugar phosphotransferase system complex genes and intact Embden-Meyerhof-Parnas pathway and hexose monophosphate pathway enzyme genes, as well as abundant carbohydrate active enzyme genes, were identified in the L. plantarum Y44 genome. We also identified genes related to the biosynthesis of exopolysaccharide and surface proteins. Surface proteins played an important role in the L. plantarum Y44 adhesion to HT-29 cell monolayers, as evidenced by the removal of cell surface proteins leading to decreased adhesion capacity. The L. plantarum Y44 genome contained genes encoding chaperones, intracellular proteases, and 2-component systems, which were associated with the general stress response. Genes encoding bile salt hydrolase, F0F1-ATPase, Na+/H+-antiporter, H+/Cl- exchange transporter, cyclopropane-fatty acyl-phospholipid synthase, and alkaline shock protein were identified in the L. plantarum Y44 genome, which might explain the strain's favorable gastric and intestinal transit tolerance. Some genes associated with encoding the NADH system, glutathione system, and thioredoxin system were predicted via in silico analysis and might account for the strain's ability to scavenge reactive oxygen species. Lactobacillus plantarum Y44 was susceptive to 7 antibiotics and did not produce biogenic amines, likely due to the absence of acquired antibiotic resistance genes and amino acid decarboxylase genes. The phenotype profile of L. plantarum Y44 was associated with its genetic characteristics, indicating that strains with certain physiological functions can be screened by analyzing their phenotypic and genotypic characteristics. Lactobacillus plantarum Y44 has the potential to be used as a starter culture in fermented dairy products.
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PMID:Physiological function analysis of Lactobacillus plantarum Y44 based on genotypic and phenotypic characteristics. 3241 91