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

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.

The mechanism of action of aspirin--is there anything beyond cyclo-oxygenase?

Aspirin, today, is an established drug in the regime for the prevention of myocardial infarction, especially in high-risk groups. This use of aspirin has given it a new lease of life in its tenth decade of clinical use. Aspirin is probably the oldest synthetic drug in the Pharmacopoeias today; thus one would have imagined that understanding about the drug would have reached a zenith and if not, that at least there should be certainty about its mechanism of action. Most workers agree that aspirin inhibits the cyclo-oxygenase enzyme in the platelets leading to reduced formation of prostaglandin G2, the precursor of thromboxanes. This explanation does not appear to be complete, since the role of the platelet activating factor (PAF) seems to have been ignored. The precursor for PAF is the lysophospholipid that is almost always formed when membrane phospholipid breakdown takes place. Any effective antiplatelet drug would have to inhibit the formation and/or the action of PAF, if it were to prevent platelet aggregation. Alternatively, the pathophysiological role attributed to PAF is highly exaggerated and needs to be reassessed.