ANTIBIOTICS CLASSIFICATION (other topics)
Antibiotics can be classified in several ways. The most common method classifies them according to their action against the infecting organism. Some antibiotics attack the cell wall; some disrupt the cell membrane; and the majority inhibit the synthesis of nucleic acids and proteins, the polymers that make up the bacterial cell. Another method classifies antibiotics according to which bacterial strains they affect: staphylococcus, streptococcus, or Escherichia coli, for example. Antibiotics are also classified on the basis of chemical structure, as penicillins, cephalosporins, aminoglycosides, tetracyclines, macrolides, or sulfonamides, among others.
Most antibiotics act by selectively interfering with the synthesis of one of the large-molecule constituents of the cell—the cell wall or proteins or nucleic acids. Some, however, act by disrupting the cell membrane (see Cell Death and Growth Suppression below). Some important and clinically useful drugs interfere with the synthesis of peptidoglycan, the most important component of the cell wall. These drugs include the Β-lactam antibiotics, which are classified according to chemical structure into penicillins, cephalosporins, and carbapenems. All these antibiotics contain a Β-lactam ring as a critical part of their chemical structure, and they inhibit synthesis of peptidoglycan, an essential part of the cell wall. They do not interfere with the synthesis of other intracellular components. The continuing buildup of materials inside the cell exerts ever greater pressure on the membrane, which is no longer properly supported by peptidoglycan. The membrane gives way, the cell contents leak out, and the bacterium dies. These antibiotics do not affect human cells because human cells do not have cell walls.
Many antibiotics operate by inhibiting the synthesis of various intracellular bacterial molecules, including DNA, RNA, ribosomes, and proteins. The synthetic sulfonamides are among the antibiotics that indirectly interfere with nucleic acid synthesis. Nucleic-acid synthesis can also be stopped by antibiotics that inhibit the enzymes that assemble these polymers—for example, DNA polymerase or RNA polymerase. Examples of such antibiotics are actinomycin, rifamicin, and rifampicin, the last two being particularly valuable in the treatment of tuberculosis. The quinolone antibiotics inhibit synthesis of an enzyme responsible for the coiling and uncoiling of the chromosome, a process necessary for DNA replication and for transcription to messenger RNA. Some antibacterials affect the assembly of messenger RNA, thus causing its genetic message to be garbled. When these faulty messages are translated, the protein products are nonfunctional. There are also other mechanisms: The tetracyclines compete with incoming transfer-RNA molecules; the aminoglycosides cause the genetic message to be misread and a defective protein to be produced; chloramphenicol prevents the linking of amino acids to the growing protein; and puromycin causes the protein chain to terminate prematurely, releasing an incomplete protein
In some species of bacteria the cell wall consists primarily of a thick layer of peptidoglycan. Other species have a much thinner layer of peptidoglycan and an outer as well as an inner membrane. When bacteria are subjected to Gram's stain, these differences in structure affect the differential staining of the bacteria with a dye called gentian violet. The differences in staining coloration (gram-positive bacteria appear purple and gram-negative bacteria appear colorless or reddish, depending on the process used) are the basis of the classification of bacteria into gram-positive (those with thick peptidoglycan) and gram-negative (those with thin peptidoglycan and an outer membrane), because the staining properties correlate with many other bacterial properties. Antibacterials can be further subdivided into narrow-spectrum and broad-spectrum agents. The narrow-spectrum penicillins act against many gram-positive bacteria. Aminoglycosides, also narrow-spectrum, act against many gram-negative as well as some gram-positive bacteria. The tetracyclines and chloramphenicols are both broad-spectrum drugs because they are effective against both gram-positive and gram-negative bacteria.
Antibiotics may also be classed as bactericidal (killing bacteria) or bacteriostatic (stopping bacterial growth and multiplication). Bacteriostatic drugs are nonetheless effective because bacteria that are prevented from growing will die off after a time or be killed by the defense mechanisms of the host. The tetracyclines and the sulfonamides are among the bacteriostatic antiobiotics. Antibiotics that damage the cell membrane cause the cell's metabolites to leak out, thus killing the organism. Such compounds, including penicillins and cephalosporins, are therefore classed as bactericidal.
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