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

Focal infections such as chronic tonsillitis or dental caries occasionally play a role in the induction or exacerbation of palmoplantar pustulosis (PPP). Arthro-osteitis is sometimes a complication in severe cases of PPP. To study the effects of bacterial infection on the exacerbation of cutaneous lesions and arthralgia, we investigated the T-cell receptor V beta repertoire in peripheral blood mononuclear cells (PBMC) and tonsil tissue after tonsillectomy in 4 cases, who had chronic tonsillitis and a history of exacerbation of cutaneous lesions following a sore throat. First, serum levels of interleukin-6 (IL-6) and IL-8 were measured before and after tonsillectomy by enzyme-linked immunosorbent assay (ELISA). Second, 3H-TdR incorporation was used to examine the effects of the culture supernatant on the PBMC of the autologous patients, other PPP patients without tonsillitis and normal controls. T-cell receptor V beta repertoire was examined by the reverse transcriptase-polymerase chain reaction method. Results showed that IL-8 was significantly high in the serum and abundantly released from tonsillar lymphocytes, which may play a role in the accumulation of neutrophils in lesional skin. T-cell receptors V beta 6 and 12 were preferentially expressed on tonsillar lymphocytes, and V beta 4, 7, 9, 17 and 18 were detected relatively frequently. These data suggest that restricted usage of T-cell receptor V beta subsets may play a crucial role in the induction of tonsillitis associated with PPP.
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PMID:Restricted usage of the T-cell receptor V beta repertoire in tonsillitis in association with palmoplantar pustulosis. 960 17

The molecular immune response of the pulpal tissue during chronic carious infection is poorly characterized. Our objective was to examine the expression of potential molecular mediators of pulpal inflammation, correlate their levels with disease severity, and determine the cellular localization of key molecules. Results indicated that there was significantly increased transcriptional activity in carious compared to healthy pulp, and the increase correlated positively with disease severity. Semiquantitative reverse transcriptase PCR analysis in 10 carious and 10 healthy pulpal tissue samples of the S100 family members S100A8, S100A9, S100A10, S100A12, and S100A13; the cytokines tumor necrosis factor alpha (TNF-alpha), interleukin-1beta (IL-1beta), IL-8, IL-6, and epithelial cell-derived neutrophil attractant 78 (ENA-78); and the structural protein collagen-1alpha indicated that all genes tested, with the exception of S100A10, were more abundantly expressed in carious teeth. In addition, we found that the closer the carious lesion front was to the pulpal chamber the higher the expression was for all genes except S100A10. Multiple-regression analysis identified a significant positive correlation between the expression levels of S100A8 and IL-1beta, ENA-78, and IL-6 and between collagen-1alpha and S100A8, TNF-alpha, IL-1beta, IL-8, IL-6, and ENA-78. Immunohistochemical studies in carious pulpal tissue indicated that S100A8 and the S100A8/S100A9 complex were predominantly expressed by infiltrating neutrophils. Gene expression analyses in immune system cells supported these findings and indicated that bacterial activation of neutrophils caused upregulation of S100A8, S100A9, and S100A13. This study highlights the complex nature of the molecular immune response that occurs during carious infection.
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PMID:S100 and cytokine expression in caries. 1521 55

The biofilm-forming Streptococcus mutans is a gram-positive bacterium that resides in the human oral cavity and is considered to be the primary etiological agent in the formation of dental caries. The global response regulator CovR, which lacks a cognate sensor kinase, is essential for the pathogenesis and biofilm formation of this bacterium, but it is not clear how covR expression is regulated in S. mutans. In this communication, we present the results of our studies examining various factors that regulate the expression of covR in S. mutans UA159. The results of Southern hybridization and PCR analysis indicated that CovR is an orphan response regulator in various isolates of S. mutans. The transcriptional start site for covR was found to be 221 base pairs upstream of the ATG start codon, and site-directed mutagenesis of the upstream TATAAT box confirmed our findings. The expression of covR is growth phase dependent, with maximal expression observed during exponential-growth phase. While changes to the growth temperature did not significantly affect the expression of covR, increasing the pH or the concentration of Mg(2+) in the growth medium leads to an increase in covR expression. The results of semiquantitative reverse transcriptase PCR analysis and in vivo transcriptional-fusion reporter assays indicated that CovR autoregulates its own expression; this was verified by the results of electrophoretic mobility shift assays and DNase I protection assays, which demonstrated direct binding of CovR to the promoter region. Apparently, regulation by Mg(2+) and the autoregulation of covR are not linked. A detailed analysis of the regulation of CovR may lead to a better understanding of the pathogenesis of S. mutans, as well as providing further insight into the prevention of dental caries.
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PMID:Modulation of covR expression in Streptococcus mutans UA159. 1846 11

The molecular alarmone (p)ppGpp functions as a global regulator of gene expression in bacteria. In Streptococcus mutans, (p)ppGpp synthesis is catalyzed by three gene products: RelA, RelP, and RelQ. RelA is responsible for (p)ppGpp production during a stringent response, and RelP is the primary source of (p)ppGpp during exponential growth, but the role of RelQ has not been thoroughly investigated. In this study, we analyzed the four-gene relQ operon to establish how these gene products may affect homeostasis and stress tolerance in the dental caries pathogen S. mutans. Northern blotting and reverse transcriptase PCR demonstrated that relQ is cotranscribed with the downstream genes ppnK (NAD kinase), rluE (pseudouridine synthase), and pta (phosphotransacetylase). In addition, a promoter located within the rluE gene was shown to drive transcription of pta. Inactivation of relQ, ppnK, or rluE did not significantly affect growth of or stress tolerance by S. mutans, whereas strains lacking pta were more sensitive to acid and oxidative stresses. Interestingly, introduction of an rluE deletion into the pta mutant reversed the deleterious effects of the pta mutation on growth and stress tolerance. Accumulation of (p)ppGpp was also decreased in a pta mutant strain, whereas inactivation of relQ caused enhanced (p)ppGpp synthesis in exponential-phase cells. The results reveal an important role for the relQ operon in the expression of traits that are essential for persistence and pathogenesis by S. mutans and provide evidence for a molecular connection of acetate and (p)ppGpp metabolism with tolerance of acid and oxidative stresses.
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PMID:Transcriptional organization and physiological contributions of the relQ operon of Streptococcus mutans. 2234 97

Streptococcus mutans is a commensal member of the healthy plaque biofilm and the primary causative agent of dental caries. The present study is an investigation of SloR, a 25-kDa metalloregulatory protein that modulates genes responsible for S. mutans-induced cariogenesis. Previous studies of SloR homologues in other bacterial pathogens have identified three domains critical to repressor functionality: an N-terminal DNA-binding domain, a central dimerization domain, and a C-terminal FeoA (previously SH3-like) domain. We used site-directed mutagenesis to identify critical amino acid residues within each of these domains of the SloR protein. Select residues were targeted for mutagenesis, and nonconservative amino acid substitutions were introduced by overlap extension PCR. Furthermore, three C-terminally truncated SloR variants were generated using conventional PCR. The repressor functionality and DNA-binding ability of each variant was assessed using CAT reporter gene assays, real-time semiquantitative reverse transcriptase (qRT)-PCR, and electrophoretic mobility shift assays. We identified 12 residues within SloR that cause significant derepression of sloABC promoter activity (P < 0.05) compared to the results for wild-type SloR. Derepression was particularly noteworthy in metal ion-binding site 1 mutants, consistent with the site's importance in gene repression by SloR. In addition, a hyperactive SloR(E169A/Q170A) mutant was identified as having significantly heightened repression of sloABC promoter activity, and experiments with C-terminal deletion mutants support involvement of the FeoA domain in SloR-mediated gene repression. Given these results, we describe the functional domains of the S. mutans SloR protein and propose that the hyperactive mutant could serve as a target for rational drug design aimed at repressing SloR-mediated virulence gene expression.
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PMID:Characterization of the functional domains of the SloR metalloregulatory protein in Streptococcus mutans. 2310 11