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interrupt folic acid biosynthesis in bacteria which prevents DNA synthesis

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  1. interrupt folic acid biosynthesis in bacteria which prevents DNA synthesis. Bactericidal.
  2. Inhibit bacterial DNA synthesis by inhibiting DNA gyrase and Topoisomerase IV enzymes.
  3. Damages bacterial DNA by binding to ribosomal proteins, inhibiting respiration and pyruvate metabolism.
  4. enters bacterial cells through a glycerophosphate transporter & inhibits the enzyme MurA, which is involved in peptidoglycan synthesis. This cell wall synthesis is blocked at an earlier step than is inhibited by beta-lactams.
  5. is converted to formaldehyde, which has a direct antiseptic action (reaction requires acidic urine <5.5).
  6. Inhibit transpeptidase activity by binding to the transpeptidase enzyme and forming a penicilloyl intermediate that slowly hydrolyzes and by binding to PBPs on maturing peptidoglycan strands (this decreases peptidoglycan synthesis and increases autolysins which lead to lysis and cell death).
  7. diffuse through porin channels in the outer membrane of gram-negative bacteria. The transport depends on an oxygen-dependent electron transport system. Binding to the 30S ribosome causes misreading and premature termination of mRNA translation, resulting in production of incompletely synthesized proteins and abnormal/nonfunctional proteins (misfolding) which leads to altered permeability and increased aminoglycoside uptake and leakage of intracellular components.

 

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