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Genomic Loss of Penicillin-Binding Protein 3 in Burkholderia pseudomallei Confers Clinical Resistance to Ceftazidime

ABSTRACT: Array-CGH analysis and Burkholderia pseudomallei isolates pre and post ceftazidime relapse. Genomic DNA from both the parental strains and variant strains were labeled with Cy3 or Cy5 fluorescent dyes and hybridized onto a customized microarray with probes designed from the reference Bp K96243 genome. Log2 signal ratios of parental strain over the variant strains were then computed after normalization to find genomic loss or gain in the variant strains.

ORGANISM(S): Burkholderia pseudomallei

SUBMITTER: Wen Fong Ooi

PROVIDER: E-GEOD-25832 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Antimicrobial resistance to ceftazidime involving loss of penicillin-binding protein 3 in Burkholderia pseudomallei.

Chantratita Narisara N Rholl Drew A DA Sim Bernice B Wuthiekanun Vanaporn V Limmathurotsakul Direk D Amornchai Premjit P Thanwisai Aunchalee A Chua Hui Hoon HH Ooi Wen Fong WF Holden Matthew T G MT Day Nicholas P NP Tan Patrick P Schweizer Herbert P HP Peacock Sharon J SJ

Proceedings of the National Academy of Sciences of the United States of America 20111003 41

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 cefta ...[more]

PMID: 21969582

Similar Datasets

Genomic Loss of Penicillin-Binding Protein 3 in Burkholderia pseudomallei Confers Clinical Resistance to Ceftazidime

Project description:Array-CGH analysis and Burkholderia pseudomallei isolates pre and post ceftazidime relapse.

2011-10-07 | GSE25832 | GEO

Transcriptomics analysis during the transient ceftazidime tolerance of Burkholderia pseudomallei

Project description:B. pseudomallei strain K96243 is sensitive to the drug ceftazidime (CAZ), but has been shown to exhibit transient CAZ tolerance when in a biofilm form. To investigate an observed shift in gene expression profile during ceftazidime (CAZ) tolerance and to better understand the mechanistic aspects of this transient tolerance, RNA-sequencing was performed on B. pseudomallei K96243 from the following three growth states: planktonic-free, biofilm, and planktonic shedding cells. Results indicated that the expression of 651 genes (10.97%) were significantly changed in both biofilm (resistant) and planktonic shedding (sensitive) cells in comparison to the planktonic state. Burkholderia biofilm shifts its transcriptome in response to ceftazidime exposure by regulating iron-sulfur stabilizing and metabolic-related genes.

2021-06-30 | GSE168275 | GEO

B. pseudomallei K96243 genome: Control vs. B. pseudomallei environmental or clinical isolates

Project description:To use whole genome microarrays to compare the differences in genome contents of 5 B. pseudomallei isolated from clinical specimens and environmental sample with B. pseudomallei K96243 reference strain and reveals variable patterns of Genomic Islands (GIs) Keywords: Comparative genomic hybridization DNA microarrays were used to compare genome of clinical and environmental B. pseudomallei isolates with B. pseudomallei K96243 reference strain (B. pseudomallei K96243 vs. B. pseudmallei isolates). Each hybridization was used for comparison between B. pseudomallei K96243 as a reference strain with environmental isolate BP45s, environmental isolate BP28L, clinical isolate H307, clinical isolate P54, clinical isolate P82. Two replicate per array. Multiple hits with 90-99.99 % identity correspond to other locus are replicate of their genes were averaged and analyzed.

2012-07-30 | E-GEOD-19558 | biostudies-arrayexpress

B. pseudomallei K96243 genome: Control vs. B. pseudomallei environmental or clinical isolates

2012-07-31 | GSE19558 | GEO

Overexpression of the AraC-type regulator HrpBbp in B. pseudomallei

Project description:The AraC-type regulator encoded by locus tag BPSS1610 is overexpressed in Burkholderia pseudomallei to identify the genes it regulates.

2011-03-01 | E-MTAB-484 | biostudies-arrayexpress

The Condition-Dependent Transcriptional Landscape of Burkholderia pseudomallei

Project description:Bacterial transcriptomes are dynamic, context-specific and condition-dependent. Infection by the soil bacterium, Burkholderia pseudomallei, causes melioidosis, an often fatal infectious disease of humans and animals. Possessing a large multi-chromosomal genome, B. pseudomallei is able to persist and survive in a multitude of environments. To obtain a comprehensive overview of B. pseudomallei expressed transcripts, we initiated whole-genome transcriptome profiling covering a broad spectrum of conditions and exposures M-bM-^@M-^S a so-called M-bM-^@M-^\condition compendiumM-bM-^@M-^]. Using the compendium, we confirmed many previously-annotated genes and operons, and also identified hundreds of novel transcripts including anti-sense transcripts and non-coding RNAs. By systematically examining genes exhibiting highly similar expression patterns, we ascribed putative functions to previously uncharacterized genes, and identified novel regulatory elements controlling these expression patterns. We also used the compendium to elucidate candidate virulence pathways associated with quorum-sensing and infection in mice. Our study showcases the power of a B. pseudomallei condition compendium as a valuable resource for understanding microbial physiology and the pathogenesis of melioidosis. The transcriptome profiles of Bp exposed to 82 conditions were captured using a custom-designed tiling microarray and compiled into a compendium revealing novel genomic features and co-expression network.

2013-09-12 | E-GEOD-43205 | biostudies-arrayexpress

Characterisation of Burkholderia pseudomallei colony morphology variants by microarray

Project description:Burkholderia pseudomallei is the causative agent of melioidosis which is endemic to Southeast Asia and Northern Australia. It is a Gram-negative soil and water bacterium that represents a potential bioterrorism threat. Colony morphology variation is a remarkable feature in primary clinical cultures of B. pseudomallei. Differences in expression of several potential virulence and survival genes were believed to be associated with B. pseudomallei colony morphology variants. Microarrray approach was used to investigate alterations of the global B. pseudomallei transcriptome profile at the mid-logarithmic phase of growth, among the wild type (WT) and small colony variant (SCV) of B. pseudomallei pre- and post-exposed to human lung epithelial cells, A549. Generally, SCV pre- and post-exposed have lower metabolic requirements and consume lesser energy than WT pre- and post-exposed to A549; however, both WT and SCV may limit their metabolic activity during the infection of A549 cells and this is indicated by the down-regulation of genes implicated in metabolism of amino acids, carbohydrate, lipid, and other amino acids, and biodegradation of xenobiotics. On the other hand, many well-known virulence and survival factors including T3SS, T6SS, fimbriae, capsular polysaccharides, drug resistance and stress response were up-regulated in both WT and SCV pre- and post-exposed to A549 cells. Several virulence factors expressed at the mid-logarithmic phase of growth. Microarray analysis on the different morphotypes demonstrated the essential difference in bacterial response associated with virulence and survival pre- and post-exposed to A549 cells.

2016-10-12 | GSE87827 | GEO

Transcription profiling of C. elegans infected with Burkholdeia pseudomallei

Project description:Worms infected with B. pseudomallei. <br> Infections performed by David O'Callaghan.

2010-11-28 | E-MEXP-1365 | biostudies-arrayexpress

Global transcriptional study of Burkholderia pseudomallei wild type and ∆BPSS1356 mutant strains

Project description:This study describes the global transcriptional changes upon deletion of a hypothetical gene BPSS1356. The BPSS1356 deletion strain of B. pseudomallei was generated via homologous recombination. Global gene expression profiling of wild type and ∆BPSS1356 mutant strains was performed to elucidate of biological functions of BPSS1356.

2013-12-31 | GSE53710 | GEO

Comparison of the transcriptomes of a Burkholeria pseudomallei bprR [bpss0688] mutant, a bprS [bpss0687] mutant and a bprRS double mutant with the wild-type B. pseudomallei K96243 parent strain.

Project description:Objectives: The Burkholderia pseudomallei bprR and bprS genes are predicted to encode the response regulator and sensor kinase components respectively of a two component signal transduction system. Inactivation of either single component of this two component signal transduction system led to attenuation of B. pseudomallei virulence and also reduced motility. However, inactivation of both components resulted in wild-tpe virulence and motility. Therefore, we used RNA-seq to compare the transcritptomes of the three mutant strains (bprR single, bprS single, bprRS double mutant) with the wild-type parent strain in order to identify the genes differenty regulated in the different mutants.

2016-04-27 | GSE77970 | GEO

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