Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.49 (reverse transcriptase)
 31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We characterized the expression of a putative toxin of Bacillus anthracis, a member of the cholesterol-dependent cytolysin (CDC) family, which includes listeriolysin O, perfringolysin O, and streptolysin O. We named this cytotoxin anthrolysin O (ALO). Although B. anthracis expresses minimal hemolytic activity in clinical settings, we show that Sterne strain 7702 expresses hemolytic activity when grown in brain heart infusion broth or in other rich bacteriologic media, but it secretes barely detectable amounts of hemolysin when grown in Luria-Bertani (LB) broth. Glucose supplementation of LB broth increases the amount of secreted hemolytic activity. Expression of hemolytic activity is maximal during mid- to late-log phase and decreases in the stationary phase. These observations are supported, in part, by semiquantitative reverse transcriptase PCR of alo mRNA. Hemolytic activity in growth supernatants was increased in the presence of reducing agent and almost totally inhibited in a dose-dependent manner by cholesterol; both of these activities are characteristic of a CDC toxin. A mutant of Sterne strain 7702, strain UT231, in which the alo gene was deleted and replaced by a kanamycin cassette, secreted barely detectable hemolytic activity into the growth medium. When strain UT231 was complemented in trans with native alo on a low-copy-number plasmid [strain UT231(pUTE554)], it regained the ability to secrete hemolytic activity, indicating that ALO is the major hemolysin secreted by this strain of B. anthracis in rich media in vitro. To further support the alo gene product being a hemolysin, recombinant B. anthracis ALO (rALO) purified from Escherichia coli was extremely active against washed human erythrocytes, with complete hemolysis detected at approximately 30 molecules of rALO per erythrocyte. Considering the virulence roles of CDCs for other gram-positive bacteria, we speculate that ALO may have a role in anthrax virulence.
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PMID:Characterization of anthrolysin O, the Bacillus anthracis cholesterol-dependent cytolysin. 1276 Oct 97

Edema toxin (EdTx), which is a combination of edema factor and a binding moiety (protective antigen), is produced by Bacillus anthracis, the etiological agent of anthrax. EdTx is an adenylyl cyclase enzyme that converts adenosine triphosphate to adenosine-3',5'-monophosphate, resulting in interstitial edema seen in anthrax patients. We used GeneChip analysis to examine global transcriptional profiles of EdTx-treated RAW 264.7 murine macrophage-like cells and identified 71 and 259 genes whose expression was significantly altered by the toxin at 3 and 6h, respectively. Alteration in the expression levels of selected genes was confirmed by real time-reverse transcriptase polymerase chain reaction. The genes with up-regulated expression in macrophages in response to EdTx-treatment were known to be involved in inflammatory responses, regulation of apoptosis, adhesion, immune cell activation, and transcription regulation. Additionally, GeneChip analysis results implied that EdTx-induced activation of activator protein-1 (AP-1) and CAAAT/enhancer-binding protein-beta (C/EBP-beta). Gel shift assays were therefore performed, and an increase in the activities of both of these transcription factors was observed within 30 min. EdTx also inhibited tumor necrosis factor alpha production and crippled the phagocytic ability of the macrophages. This is the first report detailing the host cell global transcriptional responses to EdTx.
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PMID:Murine macrophage transcriptional and functional responses to Bacillus anthracis edema toxin. 1684 16

Bacillus anthracis, a bioterrorism threat as well as an agricultural concern, has complex mechanisms for regulation of its major virulence factors. Genome searches identified the putative two-component system that we designated Bacillus anthracis respiratory response (Brr)A-BrrB. A brrA deletion strain was constructed, and real-time reverse transcriptase polymerase chain reaction and Western blot analysis were used to assess the effect of BrrA-BrrB on levels of virulence factors, the regulator atxA, and growth characteristics. When brrA was deleted, the genes for anthrax toxins (lethal factor, protective antigen, and edema factor) where expressed 4-6-log10-fold less than in the parent Sterne strain. The global regulator atxA was downregulated when compared to atxA in the Sterne strain. Thus, the BrrA-BrrB two-component system positively regulates B. anthracis toxin genes as well as the atxA regulator. Aerobic growth was not affected by the DeltabrrA mutation, but colonies showed differences in morphology, the mutant did not sporulate, and the strain lost the ability to synthesize cytochrome aa3. Gel-shift mobility assays demonstrated that BrrA bound to the promoters of genes for both protective antigen and cytochrome aa3, demonstrating that BrrA is a transcription factor. BrrA-BrrB has sequence similarity with the virulence regulator SrrA-SrrB in Staphylococcus aureus and the aerobic/anaerobic regulator, ResD-ResE, in B. subtilis, and appears to share regulatory mechanisms with ResD-ResE.
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PMID:The two-component system Bacillus respiratory response A and B (BrrA-BrrB) is a virulence factor regulator in Bacillus anthracis. 1753 38

In this study, we propose a drug design approach which includes docking, molecular fingerprints based cluster analysis, and 'induced' descriptors based receptor-dependent 3D-QSAR. The method was shown to be very useful for screening and modeling structurally diverse data sets of pharmacological interest. Different from other receptor-dependent 3D-QSAR, no ambiguous alignments are required for the construction of the models, and the computational cost is relatively lower. Moreover, 'induced' descriptors were shown to be very powerful in "capturing" ligand-receptor intermolecular interactions. The methodology was validated for eight data sets sampled from the literature and from public databases: human sex hormone-binding globulin, human corticosteroid-binding globulin, anthrax lethal factor, HIV-1 reverse transcriptase, neuraminidase A, thrombin, trypsin, and Pneumocystis carinii dihydrofolate reductase data sets. The resulting models were interpretable; the constructed QSAR equations have high statistical significance and predictive strength; and the drug design solutions were shown to be useful for guiding ligand modification for the development of new inhibitors for a broad range of molecular targets.
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PMID:Using molecular docking, 3D-QSAR, and cluster analysis for screening structurally diverse data sets of pharmacological interest. 1881 24