Genetics of extended-spectrum beta-lactamases

Abstract

Bacteria have adapted to the introduction of aztreonam, cefotaxime, ceftazidime, ceftriaxone and other oxyimino-beta-lactams by altering existing plasmid-mediated class A and class D beta-lactamases so as to expand their spectrum of activity. In the TEM and SHV families of extended-spectrum beta-lactamases, relative activity toward oxyimino-substrates increases with the number of amino acid substitutions but at the price of lowered intrinsic efficiency, so that compensatory up-promoter events are often associated with increased enzyme expression. Another new mechanism of resistance is the capture on plasmids of normally chromosomal genes from Enterobacter cloacae, Citrobacter freundii or Pseudomonas aeruginosa, which upon transfer can provide Klebsiella pneumoniae or Escherichia coli with resistance to alpha-methoxy-beta-lactams, such as cefoxitin or cefotetan, as well as to oxyimino-beta-lactams.