[Mechanisms of action of beta-lactam antibiotics and mechanisms of non-enzymatic resistance].

The mode of action of beta-lactam antibiotics, and the non-enzymatic resistance mechanisms to their activity, are intimately linked to the structure and biosynthesis of the bacterial cell wall. The bacteriostatic effect of beta-lactam antibiotics is related to their various interactions and concomitant inhibition of essential enzymes (transpeptidases, carboxypeptidases) involved in the terminal stages of peptidoglycan biosynthesis. These cytoplasmic membrane-associated target enzymes bind the antibiotics covalently, and hence are known as penicillin-binding proteins (PBPs). The bactericidal effect of these antibiotics is due to a second step following on from the inhibition of cell division and growth, in which the activation of an autolytic system causes cell death. Resistance to beta-lactam antibiotics in Gram-positive bacteria, in the absence of a beta-lactamase, is due to various modifications of the PBPs. Such mechanisms are often found in enterococci, pneumococcus, ans staphylococci. With Gram-negative bacteria such modifications of PBPs are only a rare basis for resistance. The presence of an outer membrane brings another factor into the activity of beta-lactam antibiotics, which is the facility with the antibiotics can diffuse through specialised proteins termed porins. It is generally a modification of the amounts of these proteins, or some other components of the outer membrane, which causes the non-enzymatic mechanism of resistance, particularly in species such as Klebsiella, Enterobacter, Serratia and Pseudomonas.