A novel chromosomal TEM derivative and alterations in outer membrane proteins together mediate selective ceftazidime resistance in Escherichia coli.
A clinical Escherichia coli isolate (MG32) resistant to ceftazidime but susceptible to other third-generation cephalosporins was previously examined and found to harbor TEM-1 and exhibit alterations in outer membrane proteins. Reexamination of this isolate revealed the additional presence of a novel TEM-1 derivative, now designated TEM-12. Evaluation of ceftazidime and cefotaxime minimum inhibitory concentrations for isogenic derivatives demonstrated a major role for TEM-12 in the decreased susceptibility observed. This was selectively enhanced for ceftazidime resistance by the altered porins of E. coli MG32. TEM-12 appeared identical to TEM-101, an in vitro TEM derivative, in both isoelectric point (pI 5.25) and substrate profile. Hybridization and cloning of the TEM-12 determinant revealed that, unlike other TEM derivatives, TEM-12 is chromosomally encoded, not plasmid-encoded.
Department of Medical Microbiology, Creighton University School of Medicine, Omaha, Nebraska 68178.
D A
DA
Weber
C C
CC
Sanders
J S
JS
Bakken
J P
JP
Quinn
D001425:Bacterial Outer Membrane Proteins / Q000032:analysis*; D002439:Cefotaxime / Q000494:pharmacology; D002442:Ceftazidime / Q000494:pharmacology*; D002969:Clavulanic Acids / Q000494:pharmacology; D015247:Deoxyribonuclease HindIII; D004347:Drug Interactions; D004352:Drug Resistance, Microbial / Q000235:genetics; D004591:Electrophoresis, Polyacrylamide Gel; D004926:Escherichia coli / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D006801:Humans; D007525:Isoelectric Focusing; D009693:Nucleic Acid Hybridization; D011815:R Factors; D001618:beta-Lactamases / Q000235:genetics / Q000378:metabolism*
D001425:Bacterial Outer Membrane Proteins; D002969:Clavulanic Acids; D002442:Ceftazidime; D015247:Deoxyribonuclease HindIII; D001618:beta-Lactamases; C034413:beta-lactamase TEM-1; D002439:Cefotaxime