Gram-positive bacteria binding proteins

Fig. 9.1 Schematic representation of possible mechanisms of resistance in Gram-negative and Gram-positive bacteria. 1, antibiotic-inactivating enzymes 2, antibiotic efflux proteins 3, alteration or duplication of intracellular targets 4, alteration of the cell membrane reducing antibiotic uptake 5, alterations in porins or lipopolysaccharide reducing antibiotic uptake or binding.

Many antibiotics, which inhibit protein synthesis, do not bind to ribosomes but block any of a variety of vital chemical processes needed for growth. Among them are pseudomonic acid, which inhibits isoleucyl-tRNA synthetase from many gram-positive bacteria.1111/VV Rapamycin, best known as an immunosuppressant (Box 9-F), inhibits phosphoinositide-3-kinase and also phosphorylation of the cap-binding protein 4G, a component of the eukaryotic initiation factor complex (Fig. 29-11 ).ww The bacterial enzyme peptide deformylase, which is absent from the human body, has been suggested as a target for design of synthetic antibiotics. 01... 

Both gram-negative and, more recently, gram-positive bacteria (1,16,17) have been used to display various peptide libraries that were screened to find ligands (18-20), antibodies (21,22), and vaccines (23). Surface display on yeasts has produced the very popular yeast-two hybrid system and some of its variants several recent papers and reviews are referenced here (24-27). These methods have been used to prepare and select polypeptides and proteins for various applications, including the identification of binding partners in protein-protein interactions where this is the technique of choice (28-31). 

More than 500 different representatives of the macrolide antibiotics are known, most of which are biologically active against Gram-positive bacteria, displaying a relatively low toxicity. Clinically used are erythromycin, oleandomycin, carbomycin and leucomycin (O Fig. 5). They act as inhibitors of the bacterial protein biosynthesis by binding to the 50S-ribosomal subunit. The synthesis of the two clinically important 16-membered ring macrolide antibiotics leucomycin A3 and carbomycin B could be started from D-glucose, which was chosen because it contained three of the required stereocenters [40]. 

Erythromycin is indicated for the treatment of infections caused by erythromycin susceptible bacteria. The drug binds to the 50 S ribosomal subunit inhibiting bacterial RNA-dependent protein synthesis. Susceptible bacteria include most Gram-positive bacteria and the atypical pathogens. 

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