Inhibition of cell wall synthesis--is this the mechanism of action of penicillins?

Med Hypotheses. 1995 Feb;44(2):127-31. doi: 10.1016/0306-9877(95)90085-3.


Penicillins have been shown to inhibit bacterial cell wall synthesis, and interact with penicillin binding proteins, leading to bacterial lysis. These two mechanisms, the former more than the latter are believed to be responsible for their therapeutic potential. It has further been demonstrated that only actively multiplying cells are susceptible to bactericidal effects of the antibiotic, which is in accordance with the suggested mechanism of action. Bacterial growth takes place in terms of size and number, both requiring additional cell wall. An increase in bacterial size is due to an increase in the volume of cytosol and area of the cell wall. Presently there is no proof that the former is the cause of the latter or vice versa. Penicillin by inhibiting cell wall synthesis would inhibit both growth and multiplication. Since the antibiotic is bactericidal to rapidly multiplying cells, its effect on cell wall would interfere with its bactericidal action. As per the present understanding penicillin acts principally by inhibiting cell wall synthesis. There is however a discrepancy between its observed effects and what should logically be expected, which forces us to reexamine the mechanism of action of penicillin. We believe that the present understanding of the action of penicillin is incomplete if not outright faulty. It would be expedient to radically modify the same in view of its implication, for example on drug development.

MeSH terms

  • Anti-Bacterial Agents / pharmacokinetics
  • Cell Division / drug effects
  • Cell Wall / drug effects*
  • Cell Wall / metabolism
  • Gram-Negative Bacteria / drug effects*
  • Gram-Negative Bacteria / growth & development
  • Gram-Negative Bacteria / metabolism
  • Half-Life
  • Lactams
  • Models, Biological
  • Penicillin Resistance
  • Penicillins / pharmacokinetics
  • Penicillins / pharmacology*


  • Anti-Bacterial Agents
  • Lactams
  • Penicillins