Effects of Asp-179 mutations in TEMpUC19 beta-lactamase on susceptibility to beta-lactams.
To examine the effect of disruption of the salt bridge (between Arg-164 and Asp-179 [numbering of Ambler et al. (Biochem J. 267:269-272, 1991)]) that anchors the conserved omega-loop in class A beta-lactamases, we obtained mutant enzymes with each of the 19 other amino acid residues replacing Asp-179 in the TEM beta-lactamase encoded by pUC19 and studied the level of resistance to various beta-lactams conferred by each enzyme. All mutations of Asp-179 compromised the level of resistance to ampicillin, but most of them enhanced resistance to ceftazidime. In contrast, mutations of Asp-179 generally impaired the low levels of resistance to cefepime and aztreonam. One might expect to find clinical isolates with mutant TEM beta-lactamases with replacements of Asp-179 that express an expanded spectrum of resistance to beta-lactams including ceftazidime.
D000668:Ampicillin Resistance / Q000235:genetics; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D018550:Cephalosporin Resistance / Q000235:genetics; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics; D008826:Microbial Sensitivity Tests; D009154:Mutation; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics*; D013462:Sulfur Radioisotopes; D018440:beta-Lactam Resistance / Q000235:genetics*; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases / Q000235:genetics*; D047090:beta-Lactams
D000900:Anti-Bacterial Agents; D013462:Sulfur Radioisotopes; D065093:beta-Lactamase Inhibitors; D047090:beta-Lactams; C096780:beta-lactamase TEM-pUC19; D001618:beta-Lactamases