Antibiotics action, site

These organelles, the sites of protein synthesis, are well-established targets for antibiotic action. 

The (3-lactam antibiotics structurally resemble the terminal D-alanyl-D-alanine (o-Ala-o-Ala) in the pen-tapeptides on peptidoglycan (murein) (Fig. 45.1). Bacterial transpeptidases covalently bind the (3-lactam antibiotics at the enzyme active site, and the resultant acyl enzyme molecule is stable and inactive. The intact (3-lactam ring is required for antibiotic action. The (3-lactam ring modifies the active serine site on transpeptidases and blocks further enzyme function. 

L. Belova, T. Tenson, L. Xiong, P.M. McNicholas, and A.S. Mankin. 2001. A novel site of antibiotic action in the ribosome Interaction of evemimicin with the large ribosomal subunit Proc. Natl. Acad. Sci. USA 98 3726-3731. (PubMed) (Full Text in PMC)... 

Figure 9-1. Various sites of antibiotic action in protein synthesis.

In 1962 Speyer, Basilio and I proved the validity of a hypothesis by Spotts and Stanier according to which the difference between streptomycin-sensitive, resistant and dependent E. coli. resides in the structure of their ribosomes. We established that streptomycin inhibits poly(U) directed polyphenylalanine synthesis in a fractionated cell-free protein synthesizing system only if the ribosomes in the system are taken from streptomycin-sensitive cells. These results indicated that in sensitive cells streptomycin inteiieres with ribosome action. As subsequent studies revealed, streptomycin is only one among many antibiotics whose site of action is the ribosome. 

P-Lactam antibiotics exert their antibacterial effects via acylation of a serine residue at the active site of the bacterial transpeptidases. Critical to this mechanism of action is a reactive P-lactam ring having a proximate anionic charge that is necessary for positioning the ring within the substrate binding cleft (24). 

Antibiotic Producer organism Activity Site or mode of action... 

The clinical aspects of several antibiotics such as penicillin G, cephalosporin and many other antibiotics are summarised in Table 11.1. The potential microorganisms for the production of various antibiotics and then activities on site or mode of action of the antibiotics are also listed. 

Skinner R, E Cundliffe, FJ Schmidt (1983) Site of action of a ribosomal RNA methylase responsible for resistance to erythromycin and other antibiotics. J Biol Chem 258 12702-12706. 

An antibiotic inhibits bacterial growth if it is able to reach the site of its action, interacts, and substantially inhibits the function of an essential component necessary for its growth. A given bacterial cell becomes resistant to an antibiotic if at least one of these steps is no longer operative. This can result from one of the following four biochemical mechanisms. 

On the other hand, the negatively charged Kdo-lipid A domain constitutes a target for binding of certain antibiotics, such as polymyxin B (125) and basic peptides derived from host cells such as the bactericidal/perme-ability-increasing protein (BPI) (261). In this respect the Kdo-lipid A domain constitutes a weak site of the outer membrane, rendering bacteria vulnerable to the action of cationic agents. 

ESR spectra indicated that ultrasound enhanced the penetration of 16-DS into the structurally stronger sites of the inner and outer cell membranes. The effect of ultrasound on the cell membranes was transient in that the initial membrane permeability was restored upon termination of the ultrasound treatment. These results suggested that the resistance of gram-negative bacteria to the action of hydrophobic antibiotics was caused by a low permeability of the outer cell membranes and that this resistance may be reduced by the simultaneous application of antibiotic and ultrasound. 

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