Journal Article

Outer membrane protein alterations and <i>bla</i><sub>TEM-1</sub> variants: their role in β-lactam resistance in <i>Klebsiella pneumoniae</i>

E. C. Nelson, Heidi Segal and B. Gay Elisha

in Journal of Antimicrobial Chemotherapy

Published on behalf of British Society for Antimicrobial Chemotherapy

Volume 52, issue 6, pages 899-903
Published in print December 2003 | ISSN: 0305-7453
Published online December 2003 | e-ISSN: 1460-2091 | DOI: http://dx.doi.org/10.1093/jac/dkg486
Outer membrane protein alterations and blaTEM-1 variants: their role in β-lactam resistance in Klebsiella pneumoniae

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Objectives: The aim of the study was to characterize the genetic basis of resistance to selected β-lactam antibiotics in two clinical isolates of Klebsiella pneumoniae.

Methods and results: K. pneumoniae strains were isolated from two hospitalized patients. One of the strains was resistant to amoxicillin, co-amoxiclav, cefuroxime, piperacillin and cefoxitin but susceptible to all the other cephalosporins tested. The second strain displayed a similar phenotype except that it was resistant to piperacillin/tazobactam and susceptible to cefoxitin. PCR assays and DNA sequencing showed that the cefoxitin-susceptible strain contained a novel blaTEM-1 variant downstream of the strong Pa/Pb promoter. SDS–PAGE analysis of the outer membrane proteins (OMPs) did not identify OmpK35 and suggested reduced expression of OmpK36 in this strain. Following passage in non-selective media, expression of OmpK36 was restored with a concomitant increase in cefuroxime susceptibility. A similar experimental approach identified blaTEM-1C in the cefoxitin-resistant K. pneumoniae strain. This strain was deficient in OmpK35 and OmpK36; absence of the latter protein was due to the presence of IS1 in the ompK36 regulatory region.

Conclusions: Resistance to selected β-lactams in two clinical isolates of K. pneumoniae was due to interplay between the expression of OMPs and TEM-1.

Keywords: Keywords: cefuroxime, β-lactamase, IS1, Pa/Pb

Journal Article.  3332 words.  Illustrated.

Subjects: Medical Oncology ; Critical Care

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