Antimicrobial Drug Action by D. I. Edwards

By D. I. Edwards

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Any useful antimicrobial drug acts best when the pathogen is actively growing and dividing, since it is at this stage that the organism is at its most sensitive. It follows that chemotherapy is most difficult when the organism is dormant or growing very slowly. Often these differences are reflected in the differing biochemistry of the organism. The most rapidly growing organisms are aerobic, generating a large amount of ATP for growth purposes. These organisms are far more amenable to growth than anaerobes, which usually generate about a tenth of the ATP of aerobes and consequently grow that much more slowly.

9 Structure of gramicidin S. where the arrows represents the peptide bond in the order -CO-NH-. The uniqueness of the biosynthetic mechanism lies in the fact that it does not require a ribosomal mechanism and the specificity of the process, that is the mechanism controlling the order of amino acids in the polypeptide, is determined not by transfer RNAs (tRNAs) but by the arrangement of enzymes in a multienzyme complex. This process, of necessity, means that the size and disposition of the components of the multienzyme complex determines the ultimate size of the peptides produced by a non-ribosomal mechanism.

The most rapidly growing organisms are aerobic, generating a large amount of ATP for growth purposes. These organisms are far more amenable to growth than anaerobes, which usually generate about a tenth of the ATP of aerobes and consequently grow that much more slowly. It is hardly surprising, therefore, that the most intractable diseases to antimicrobial chemotherapy are those of tuberculosis and leprosy-diseases where the bacteria grow so slowly that the incubation time may be as long as 10 years.

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