Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.30.2 (endonuclease)
 18,621 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To characterize the genetic basis of drug resistance in Mycobacterium tuberculosis in Latvia, mutations involved in rifampin (rpoB gene) and isoniazid (katG gene) resistance in DNA from 19 drug-susceptible and 51 multidrug-resistant M. tuberculosis complex isolates were analyzed. The most frequent rpoB gene mutations found by the Line Probe assay were the S531L (14 of 34 isolates), D516V (7 of 34), H526D (4 of 34), and D516Y plus P535S (4 of 34) mutations. Direct sequencing of seven isolates with unclear results from Line Probe assay showed the presence of the L533P mutation and the Q510H plus H526Y (1 of 34) and D516V plus P535S (4 of 34) double mutations, neither of which has been described previously. Single-strand conformation polymorphism analysis showed strand mobility differences between the rifampin-susceptible and -resistant samples for the D516V, H526D, and D516Y plus P535S mutations but not for the S531L mutation. Nucleotide substitution at codon 315 (AGC-->ACC) of the katG gene was found in 48 of 51 multidrug-resistant samples by sequencing. Furthermore, katG gene restriction fragment length polymorphism analysis with endonuclease AciI confirmed the nucleotide change in codon 315.
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PMID:Mutations in the rpoB and katG genes leading to drug resistance in Mycobacterium tuberculosis in Latvia. 1235 82

Resistance to antituberculous agents is an important cause of ineffectiveness of antimicrobial therapy. The resistance of M. tuberculosis to antituberculous agents is a result of mutations in genes participating in those agent's action. The antituberculous drug--isoniazid can be activated by Mycobacterium tuberculosis either through a hydroperoxidase I/II or a superoxide-dependent oxyferrous pathway. The present study analyzed the frequency of the mutations occurring in codons 315 and 463 in katG gene of Mycobacterium tuberculosis strains, isolated from patients with pulmonary tuberculosis from Silesia, Poland. In this study 23 isoniazid-resistant Mycobacterium tuberculosis strains were analyzed. For RFLP analysis, a 620 bp amplified fragment of katG gene was digested with restriction endonuclease MspI. Among 24 isoniazid-resistant strains, isolated from patients between 2000-2001, point mutations were found in 30% of analyzed isoniazid-resistant strains in codons 315 or 463 (7 strains). In contrast, no mutations in codons 315 and/or 463 katG gene were found in 16 strains (70%). Obtained results suggests that point mutations S315T (AGC-->ACC) and R463L in katG gene are infrequent in the analyzed population.
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PMID:PCR-RFLP analysis of a point mutation in codons 315 and 463 of the katG gene of Mycobacterium tuberculosis isolated from patients in Silesia, Poland. 1547 53

The patient was a 34-year-old man with life-long bleeding episodes, whose hemorrhage problem was characterized predominantly by prolonged bleeding at surgical or traumatic sites. All routine coagulation parameters were within normal ranges. The patient's bleeding tendency was not caused by factor XIII deficiency, alpha2-antiplasmin deficiency, or tissue type-plasminogen activator increase. His characteristic abnormalities of fibrinolysis included shortened euglobulin clot lysis time, low plasminogen activator inhibitor-1 (PAI-1) activity and antigen in plasma, which were remarkably reduced to only about 10% of control. An operation was performed in order to clear two hematomas in the patient's left leg and hip, and subsequent bleeding episodes were well controlled with adjuvant administration of intravenous aminomethylbenoic acid after surgery. PAI-1 gene analysis by polymerase chain reaction product sequencing revealed that the patient had a heterozygous missense mutation G to A transition at nucleotide position 4497 in exon 2, causing replacement of alanine 15 (GCC) to threonine (ACC) at signal peptide. The restriction endonuclease analysis showed that this gene mutation also existed in the patient's father, but not in his mother and 60 normal subjects. The wild-type and mutant plasmids were constructed and transiently transfected into Chinese hamster ovary cell lines; the levels of PAI-1 activity and antigen in the media of the mutant were approximately 70% of the wild type, and the levels of PAI-1 protein in cell lysates were almost equal in wild-type and mutant plasmids. These results indicate that the mutation in signal peptide may partly impair the secretion of PAI-1.
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PMID:A case of deficiency of plasma plasminogen activator inhibitor-1 related to Ala15Thr mutation in its signal peptide. 1565 May 51

In the present study, among 327 Mycobacterium tuberculosis (MTB) isolates collected from patients attending three different centres of North India, we attempted to find out the most common mutations occurring both at the Ser315 codon of katG and at the regulatory region of the mabA-inhA operon to evaluate their role for INH drug resistance in India. Out of 121 phenotypically INH-resistant MTB isolates, 88 (72.7%) were resistant to INH by genotypic methods viz., PCR-RFLP with MspI and SatI digestion and multiplex-PCR. PCR-RFLP results showed that 67 (55.4%) isolates had mutation in codon 315 of katG by SatI endonuclease. Among these, eight isolates that were found resistant by SatI PCR-RFLP were found to be sensitive by MspI PCR-RFLP. By multiplex-PCR we found 49 (40.5%), 21 (17.4%) and 10 (8.3%) isolates having AGC-->ACC substitution in katG only, mutation in inhA(C-15T) only and mutation in both respectively. Simultaneous use of both PCR-RFLP and multiplex-PCR can improve the detection rate of INH-resistant strains and may have an advantage over the liquid culture system of detecting drug resistance. These findings also enhanced our understanding about potential of resistance-related mutations in M. tuberculosis clinical isolates in India and could help in development and designing of molecular methods for revealing the drug susceptibility profiles of M. tuberculosis clinical isolates.
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PMID:Molecular characterization of INH-resistant Mycobacterium tuberculosis isolates by PCR-RFLP and multiplex-PCR in North India. 1978 22