Bacteria macrolides

Drug action and drug resistance in bacteria Macrolide antibiotics and lincomycin". Ed. S. Mitsuhashi, University Park Press, Baltimore, Maryland. 1972. 

The combined intrinsic activities of different efflux pumps play a major role for the intrinsic resistance of Gram-negative bacteria to macrolides and oxazolidi-nones as well as to the intrinsic resistance of Pseudomonas aeruginosa against a broad range of disinfectants and antibiotics. 

O-phosphotransferases that modify macrolides are produced by highly macrolide resistant E. coli isolates. However, these enzymes have no clinical importance for macrolide resistance in gram-positive bacteria, and gram-negative ones are regarded as naturally resistant [2]. 

The tetracyclines exert their effect by inhibiting bacterial protein syndiesis, which is a process necessary for reproduction of die microorganism. The ultimate effect of diis action is tiiat the bacteria are either destroyed or dieir multiplication rate is slowed. The tetracyclines are bacteriostatic (capable of slowing or retarding die multiplication of bacteria), whereas die macrolides and lincosamides may be bacteriostatic or bactericidal (capable of destroying bacteria). 

The macrolides are bacteriostatic or bactericidal in susceptible bacteria The drugs act by binding to cell membranes and causing changes in protein function. 

The natural products Mycoticin A (22, R = H) and B (22, R = Me) belong to the skipped-polyol-polyene class of antibiotics. Our analytical interest here is to use this very complex molecular structure to demonstrate some of the tools employed, mainly for the elucidation of the polyene part of the molecule. This family of polyene macrolide class was discovered in 195045 with the finding of Nystatin (23), which is produced by the Streptomyces bacteria. The exact structure was elucidated only in 1970 by Chong and Rickards46 and, in 1971, Nystatin Ai (23) and A2 (not shown in this review) were separated. 

The fight against infectious pathogenic bacteria is ongoing. The principal weapons in this battle include a variety of f-lactam antibiotics as well as quinolines, tetracyclines, macrolides, and aminoglycosides. 

Macrolides, both erythromycin and others, inhibit the synthesis of bacterial proteins. The primary mechanisms of protein synthesis are identical in humans and bacteria. However, there is a significant difference that allows a specific antibiotic to exhibit selective toxicity with respect to bacteria. 

Antibacterial activity of macrolides depends on the acidity of the medium. High activity is observed in neutral and basic media in comparison with acid. In particular, erythromycin is inactivated in the acidic medium of the stomach. Macrolides have a relatively broad spectrum of use, and they are active with respect to Gram-positive and Gram-negative microorganisms, achiomycetes, mycoplasma, spirochaeta, chlamydia. Bacteria Rickettsia, certain mycobacteria. Colon bacillus, blue-pus bacillus, shigella, salmonella, and so on. 

Ansamycins, like the macrolides, are synthesized by condensation of a number of acetate and propionate units. These antibiotics, which are produced by several genera of the Actinomy-cetales, display a characteristic core aromatic ring structure. Amongst the best-known family members are the rifamycins, which are particularly active against Gram-positive bacteria and mycobacteria. They have been used, for example, in the treatment of Mycobacterium tuberculosis. 

Resistance can occur via plasmid-mediated meth-ylation of the receptor site which reduces the binding of the macrolide. Also plasmid-mediated esterase activity, especially in coliform bacteria, can inactivate the macrolides. 

Macrolides bind to the SOS ribosomal subunit of bacteria but not to the SOS mammalian ribosome this accounts for its selective toxicity. Binding to the ribosome occurs at a site near peptidyltransferase, with a resultant inhibition of translocation, peptide bond formation, and release of oligopeptidyl tRNA. However, unlike chloramphenicol, the macrolides do not inhibit protein synthesis by intact mitochondria, and this suggests that the mitochondrial membrane is not permeable to erythromycin. 

Bacteria overall > 410 Groom, 1992 Scarce diversification between land and sea. ALKAL. indole, phenazine, pyperazine, pyrrole, polypyrrole. PEPT. various classes, including siderophores. POLYKET. lactones, macrolides, quinones. CARBOH. (amino)glycoside, terpenoids hi hi ... 

Macrolide antibiotics target the bacterial ribosome and inhibit the bacterial protein biosynthesis. Many gram-negative bacteria are inherently resistant to mac-rolides because their outer membrane is impermeable to macrolides. Several mechanisms of acquired resistance have been reported. In some cases, resistance is conferred by methylation of ribosomes by methylase enzymes, the genes of... 

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