Mechanisms of resistance to cephalosporin antibiotics

Drugs
D M Livermore

Abstract

Cephalosporins, like other beta-lactams, bind to the bacterial penicillin-binding proteins (PBPs). These correspond to the D-ala-D-ala trans-, carboxy- and endo-peptidases responsible for catalysing the cross-linking of newly formed peptidoglycan. Resistance arises when the PBPs-and particularly the transpeptidases-are modified, or when they are protected by beta-lactamases or 'permeability barriers'. Target-mediated cephalosporin resistance can involve either reduced affinity of an existing PBP component, or the acquisition of a supplementary beta-lactam-insensitive PBP. beta-lactamases are produced widely by bacteria and may be determined by chromosomal or plasmid DNA. The chromosomal beta-lactamases are species-specific, but can be classified into a few broad groups. The plasmid-mediated enzymes cross interspecific and intergeneric boundaries. The level of beta-lactamase-mediated resistance relates to the amount of enzyme produced with or without induction; to the location of the enzyme (extracellular for Gram-positive organisms and periplasmic in Gram-negative ones); and to the kinetics of the enzyme's activity. In Gram-positive organisms the PBPs are located on the outer aspect of the cytoplasmic membrane and so shielding ...Continue Reading

Citations

Oct 5, 2011·Proceedings of the National Academy of Sciences of the United States of America·Narisara ChantratitaSharon J Peacock
Jan 1, 1989·Scandinavian Journal of Infectious Diseases·S HuovinenP Huovinen
Feb 23, 2010·Enfermedades infecciosas y microbiología clínica·Cristina Seral GarcíaFrancisco Javier Castillo García
Jan 30, 2015·Jundishapur Journal of Microbiology·Mohammad Najafi MoslehGiti Kalantarian
Sep 13, 2016·Clinical & Experimental Ophthalmology·Vivek Pravin DaveTaraprasad Das
Jun 19, 1989·The Medical Journal of Australia·R C Pritchard
May 10, 2019·The Journal of Physical Chemistry. B·Alessio AtzoriPaolo Ruggerone

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