RNA, bacterial ribosomal

Resistance to erythromycin is becoming a serious clinical problem. For example, most strains of staphylococci in hospital isolates are resistant to this drug. Several mechanisms have been identified (1) the inability of the organism to take up the antibiotic (2) a decreased affinity of the 50S ribosomal subunit for the antibiotic resulting from the methylation of an adenine of the 23S bacterial ribosomal RNA and (3) presence of a plasmid-associated erythromycin esterase. Both clarithromycin and azithromycin show cross-resistance with erythromycin. 

Shine, J. Dalgamo, L. (1975). Terminal-sequence analysis of bacterial ribosomal RNA. Correlation between the 3 -tenninal-polypyrimidine sequence of 16-S RNA and translational specificity of the ribosome. Eur J Biochem 57,221-30. 

B3. Bottger, E. C., Rapid determination of bacterial ribosomal RNA sequences by direct sequencing of enzymically amplified DNA. FEMS Microbiol. Lett. 65, 171-176 (1989). 

The RNA world hypothesis proposes that RNA-based living systems predated current DNA-based life. Individual RNAs, which can store information like DNA and furthermore catalyze reactions virtually like protein enzymes, may have supported cellular and/or precellular life. The naturally occurring catalytic RNA molecules are highly specific such as the small subunit bacterial ribosomal RNA that is active as a RNA peptidyl transferase. In general, ribozymes seem to be relics from the RNA world. Many different synthetic ribozymes produced in the laboratory have diverse but defined specificities. The specificity of ribozymes is due to the intrinsic chiral centers of the RNA molecules of secondary and tertiary structure. The main evidence for an RNA world is the three essential RNA classes that act in concert to direct the specific and successive biosynthesis of proteins tRNA, rRNA, and mRNA. 

Chaney, R., Rider, J., and Pamphilon, D. (1999) Direct detection of bacteria in cellular blood products using bacterial ribosomal RNA-directed probes coupled to electrochemiluminescence. Transfus Med. 9, 177-188... 

Sulfur-metabolising organisms have been monitored within the timbers of the Mary Rose by extraction and analysis of bacterial ribosomal RNA. The... 

FIGURE 46-1 Inhibition of bacterial protein synthesis by tetracyclines. Messenger RNA (mRNA) attaches to the 30S subunit of bacterial ribosomal RNA. The P (peptidyl) site of the 50S ribosomal RNA subunit contains the nascent polypeptide chain normally, the aminoacyl tRNA charged with the next amino acid (aa) to be added to the chain moves into the A (acceptor) site, with complementary base pairing between the anticodon sequence of tRNA and the codon sequence of mRNA. Tetracyclines inhibit bacterial protein synthesis by binding to the 30S subunit and blocking tRNA binding to the A site. 

Kohne, D. E. 1968. Isolation and characterization of bacterial ribosomal RNA dstrons. Carnegie Inst. Year Book, 67 310-320. 

This second type of structured region, which is thermally more stable than the first class owing to the excess of G C pairs, is not the same in aU rRNA and appears to be a function of the source. Thus in animal rRNA this second class of structured region contains about 85% of the total number of pairs as G C, whereas in bacterial ribosomal RNA ( . coli) the percentage of G - C pairs is about 67% (Cox, 1966). It is also of interest that Seeber et al. (1971), studying the polypurine sequences of nucleolar 28 S RNA from rat ascites cells, have found different octanucleotides from those reported for bacterial RNA by Nomura et al. (1969) and by Muxo (1970). Thus some differences between rRNA from animal and bacterial species do exist, but it cannot be stated that these differences alone explain the results obtained with anti-poly G poly C sera. 

Mechanism of Action. THie earliest studies on the mechanism of action of lincomycin showed that lincomycin had the immediate effect on Staphjlococcus aureus of complete inhibition of protein synthesis (23). TThis inhibition results from the blocking of the peptidyltransferase site of the SOS subunit of the bacterial ribosome (24). Litde effect on DNA and RNA synthesis was observed. 

Good L., Nielsen P.E. Inhibition of translation and bacterial growth by peptide nucleic acid targeted to ribosomal RNA. Proc. Natl Acad. Sci. USA 1998 95 2073-2076. 

Ribosomes in bacteria and in the mitochondria of higher eukaryotic cells differ from the mammalian ribosome described in Ghapter 35. The bacterial ribosome is smaller (70S rather than SOS) and has a different, somewhat simpler complement of RNA and protein... 

Bacterial ribosomes contain three RNA molecules the 5 S, 16 S, and 23 S RNAs. The nucleotide sequence of the 5 S RNA with 120 nucleo-... 

Linezohd (Zyvox) is an oxazolidinone, a tive-membered heterocychc ring that forms the core of the hnezohd structure. The approval of hnezohd by the FDA in 2000 marked the first new structural class of antibacterial introduced into medical practice in the United States in 40 years. It is notable for its activity against methicillin-resistant Staph aureus, MRSA, and vancomycin-resistant Enterococcus faecium, VRE. It is bacteriostatic rather than bactericidal but finds significant use in patients with an intact immune system. Like several other classes of antibacterials, linezolid is an inhibitor of protein synthesis. It interacts specifically with the RNA component of a bacterial ribosome subunit to prevent initiation of protein synthesis. 

Cellular RNAs vary widely in their size, structure, and lifespan. The great majority of them are ribosomal RNA (rRNA), which in several forms is a structural and functional component of ribosomes (see p.250). Ribosomal RNA is produced from DNA by transcription in the nucleolus, and it is processed there and assembled with proteins to form ribosome subunits (see pp.208, 242). The bacterial 16S-rRNA shown in Fig. A, with 1542 nucleotides (nt), is a component of the small ribosomae subunit, while the much smaller 5S-rRNA (118 nt) is located in the large subunit. 

Vicens, Q. Westhof, E. Crystal structure of geneticin bound to a bacterial 16S ribosomal RNA A site oligonucleotide. J. Mol. Biol. 2003, 326, 1175-1188. 

Bacterial resistance to erythromycin can originate by two possible mechanisms the inability of reaching the cell membrane, which is particularly relevant in the case of the microorganisms Enterobacteriaceae, or in the case of the presence of a methylated alanine in the 23 S ribosomal RNA of the 50 S subunit, which lowers the affinity of erythromycin to it. 

In many ways, mitochondria resemble bacteria for example, the mitochondrial ribosomal RNA genes of all eukaryotes have been traced back to the eubacteria [10]. This can explain why some antibacterial compounds with the target of inhibiting bacterial protein synthesis also inhibit mitochondrial protein synthesis [6, 11, 12], resulting in hematotoxicity. Tetracycline, chloramphemcol and some oxazolidinone antibiotics have been shown to induce hematotoxicity by inhibiting mitochondrial protein synthesis [13]. 

Inactivates bacterial ribosomal proteins leading to a loss of vital processes of synthesizing proteins, DNA, RNA, and cell wall. Also leads to the loss of aerobic energy metabolism. It has been around since the 1950s without serious emergence of resistance because of its broad-based range of modes of action. 

Mechanism of Action An oxalodinone anti-infective that binds to a site on bacterial 23S ribosomal RNA, preventing the formation of a complex that is essential for bacterial translation. Therapeutic Effect Bacteriostatic against enterococci and staphylococci bactericidal against streptococci. 

Mechanism of Action An antibacterial UTI agent that inhibits the synthesis of bacterial DNA, RNA, proteins, and cell walls by altering or inactivating ribosomal proteins. Therapeutic Effect Bacteriostatic (bactericidal at high concentrations). Pharmacokinetics Microcrystalline form rapidly and completely absorbed macrocrystalline form more slowly absorbed. Food increases absorption. Protein binding 40%. Primarily concentrated in urine and kidneys. Metabolized in most body tissues. Primarily excreted in urine. Removed by hemodialysis. Half-life 20-60 min. 

Another complex macromolecular aggregate that can reassemble from its components is the bacterial ribosome. These ribosomes are composed of 55 different proteins and by 3 different RNA molecules, and if the individual components are incubated under appropriate conditions in a test tube, they spontaneously form the original structure (Alberts et al., 1989). It is also known that even certain viruses, e.g., tobacco mosaic virus, can reassemble from the components this virus consists of a single RNA molecule contained in a protein coat composed by an array of identical protein subunits. Infective virus particles can self-assemble in a test tube from the purified components. 

Linezolid Prevents bacterial protein synthesis by binding to the 23S ribosomal RNA of 50S subunit Bacteriostatic activity against susceptible bacteria Infections caused by methicillin-resistant staphylococci and vancomycin-resistant enterococci Oral, IV hepatic clearance (half-life 6 h) dosed twice-daily Toxicity Duration-dependent bone marrow suppression, neuropathy, and optic neuritis serotonin-syndrome may occur when coadministered with other serotonergic drugs (eg, selective serotonin reuptake inhibitors)... 

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