title: [Mechanisms of action of beta-lactam antibiotics and mechanisms of non-enzymatic resistance].
abstract: 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.
mesh_terms: D000900:Anti-Bacterial Agents / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure; D002463:Cell Membrane Permeability; D004352:Drug Resistance, Microbial; D010403:Penicillin Resistance; D010457:Peptidoglycan / Q000378:metabolism; D047090:beta-Lactams
chemical_list: D000900:Anti-Bacterial Agents; D010457:Peptidoglycan; D047090:beta-Lactams
vernacular_title: Mécanismes d'action des bêta-lactamines et mécanismes de résistance non enzymatique.