Please use this identifier to cite or link to this item:
Title: Antimicrobial resistance to ceftazidime involving loss of penicillin-binding protein 3 in Burkholderia pseudomallei
Authors: Narisara Chantratita
Drew A. Rholl
Bernice Sim
Vanaporn Wuthiekanun
Direk Limmathurotsakul
Premjit Amornchai
Aunchalee Thanwisai
Hui Hoon Chua
Wen Fong Ooi
Matthew T.G. Holden
Nicholas P. Day
Patrick Tan
Herbert P. Schweizer
Sharon J. Peacock
Mahidol University
Colorado State University
Genome Institute of Singapore
Wellcome Trust
Nuffield Department of Clinical Medicine
National University of Singapore
University of Cambridge
Keywords: Multidisciplinary
Issue Date: 11-Oct-2011
Citation: Proceedings of the National Academy of Sciences of the United States of America. Vol.108, No.41 (2011), 17165-17170
Abstract: Known mechanisms of resistance to β-lactam antibiotics include β-lactamase expression, altered drug target, decreased bacterial permeability, and increased drug efflux. Here, we describe a unique mechanism of β-lactam resistance in the biothreat organism Burkholderia pseudomallei (the cause of melioidosis), associated with treatment failure during prolonged ceftazidime therapy of natural infection. Detailed comparisons of the initial ceftazidime-susceptible infecting isolate and subsequent ceftazidime-resistant variants from six patients led us to identify a common, large-scale genomic loss involving a minimum of 49 genes in all six resistant strains. Mutational analysis of wild-type B. pseudomallei demonstrated that ceftazidime resistance was due to deletion of a gene encoding a penicillin-binding protein 3 (BPSS1219) present within the region of genomic loss. The clinical ceftazidime-resistant variants failed to grow using commonly used laboratory culture media, including commercial blood cultures, rendering the variants almost undetectable in the diagnostic laboratory. Melioidosis is notoriously difficult to cure and clinical treatment failure is common in patients treated with ceftazidime, the drug of first choice across most of Southeast Asia where the majority of cases are reported. The mechanism described here represents an explanation for ceftazidime treatment failure, and may be a frequent but undetected resistance event.
ISSN: 10916490
Appears in Collections:Scopus 2011-2015

Files in This Item:
There are no files associated with this item.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.