Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.26.5 (RNase P)
 1,348 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The ribonucleoprotein enzyme RNase P catalyzes endonucleolytic 5'-maturation of tRNA primary transcripts in all domains of life. The indispensability of RNase P for bacterial cell growth and the large differences in structure and function between bacterial and eukaryotic RNase P enzymes comply with the basic requirements for a bacterial enzyme to be suitable as a potential novel drug target. We have identified RNA oligonucleotides that start to show an inhibitory effect on bacterial RNase P RNAs of the structural type A (for example, the Escherichia coli or Klebsiella pneumoniae enzymes) at subnanomolar concentrations in our in vitro precursor tRNA (ptRNA) processing assay. These oligonucleotides are directed against the so-called P15 loop region of RNase P RNA known to interact with the 3'-CCA portion of ptRNA substrates. Lead probing experiments demonstrate that a complementary RNA or DNA 14-mer fully invades the P15 loop region and thereby disrupts local structure in the catalytic core of RNase P RNA. Binding of the RNA 14-mer is essentially irreversible because of a very low dissociation rate. The association rate of this oligonucleotide is on the order of 10(4) M(-1) s(-1) and is thus comparable to those of many other artificial antisense oligonucleotides. The remarkable inhibition efficacy is attributable to the dual effect of direct interference with substrate binding to the RNase P RNA active site and induction of misfolding of the catalytic core of RNase P RNA. Based on our findings, the P15 loop region of bacterial RNase P RNAs of the structural type A can be considered the "Achilles' heel" of the ribozyme and therefore represents a promising target for combatting multiresistant bacterial pathogens.
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PMID:Antisense inhibition of Escherichia coli RNase P RNA: mechanistic aspects. 1452 23

Rapid detection of the bacterial causative agent causing sepsis must be coupled with rapid identification of the antibiotic resistant mechanism that the pathogen might possess. Real-time PCR (qPCR)-based assays have been extensively utilized in the clinical microbiology field as diagnostic tools for the rapid detection of specific nucleic acid (NA) targets. In this chapter, we will discuss the technical aspects of using an internally controlled qPCR assay for the rapid detection of Klebsiella pneumoniae carbapenemase gene (bla KPC) in positive Bactec blood culture bottles. The multiplex qPCR (bla KPC/RNase P) utilizes specific primers and probes for the detection of the bacterial carbapenem resistance mechanism, bla KPC gene, and the internal control RNase P. The internal control of the qPCR assay is vital for detecting any inhibitors that are well known to be present in the blood culture bottles. Rapid detection of the antibiotic resistant mechanism present in the bacterial pathogen causing sepsis can help in better managing patients' infection.
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PMID:Molecular detection of antibiotic resistance genes from positive blood cultures. 2531 83