Mode of Action
β-Lactam antibiotics are bacteriocidal, and act by inhibiting the synthesis of the peptidoglycan layer of bacterial cell walls. The peptidoglycan layer is important for cell wall structural integrity, especially in Gram-positive organisms, being the outermost and primary component of the wall. The final transpeptidation step in the synthesis of the peptidoglycan is facilitated by transpeptidases known as penicillin-binding proteins (PBPs). PBPs vary in their affinity for binding penicillin or other β-lactam antibiotics. The amount of PBPs varies among bacterial species.
β-Lactam antibiotics are analogues of d-alanyl-d-alanine—the terminal amino acid residues on the precursor NAM/NAG-peptide subunits of the nascent peptidoglycan layer. The structural similarity between β-lactam antibiotics and d-alanyl-d-alanine facilitates their binding to the active site of PBPs. The β-lactam nucleus of the molecule irreversibly binds to (acylates) the Ser403 residue of the PBP active site. This irreversible inhibition of the PBPs prevents the final crosslinking (transpeptidation) of the nascent peptidoglycan layer, disrupting cell wall synthesis.
β-Lactam antibiotics block not only the division of bacteria, including cyanobacteria, but also the division of cyanelles, the photosynthetic organelles of the glaucophytes, and the division of chloroplasts of bryophytes. In contrast, they have no effect on the plastids of the highly developed vascular plants. This is supporting the endosymbiotic theory and indicates an evolution of plastid division in land plants.
Under normal circumstances, peptidoglycan precursors signal a reorganisation of the bacterial cell wall and, as a consequence, trigger the activation of autolytic cell wall hydrolases. Inhibition of cross-linkage by β-lactams causes a build-up of peptidoglycan precursors, which triggers the digestion of existing peptidoglycan by autolytic hydrolases without the production of new peptidoglycan. As a result, the bactericidal action of β-lactam antibiotics is further enhanced.
Read more about this topic: Beta-lactam Antibiotic
Famous quotes containing the words mode of, mode and/or action:
“Yours of the 24th, asking “the best mode of obtaining a thorough knowledge of the law” is received. The mode is very simple, though laborious, and tedious. It is only to get the books, and read, and study them carefully.... Work, work, work, is the main thing.”
—Abraham Lincoln (1809–1865)
“Happiness is a matter of one’s most ordinary everyday mode of consciousness being busy and lively and unconcerned with self. To be damned is for one’s ordinary everyday mode of consciousness to be unremitting agonising preoccupation with self.”
—Iris Murdoch (b. 1919)
“We have seen the city; it is the gibbous
Mirrored eye of an insect. All things happen
On its balcony and are resumed within,
But the action is the cold, syrupy flow
Of a pageant.”
—John Ashbery (b. 1927)