Null
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB68306 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| Other | ||||
| ERR12255764_1.fastq.gz | Fastqsanger.gz | |||
| ERR12255764_2.fastq.gz | Fastqsanger.gz | |||
| ERR12255765_1.fastq.gz | Fastqsanger.gz | |||
| ERR12255765_2.fastq.gz | Fastqsanger.gz |
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Project description:Antibiotic use can lead to expansion of multi-drug resistant pathobionts within the gut microbiome that can cause life-threatening infections. Selective alternatives to conventional antibiotics are in dire need. Here, we describe a Klebsiella PhageBank that enables the rapid design of antimicrobial bacteriophage cocktails to treat multi-drug resistant Klebsiella pneumoniae. Using a transposon library in carbapenem-resistant K. pneumoniae, we identified host factors required for phage infection in major Klebsiella phage families. Leveraging the diversity of the PhageBank and experimental evolution strategies, we formulated combinations of phages that minimize the occurrence of phage resistance in vitro. Optimized bacteriophage cocktails selectively suppressed the burden of multi-drug resistant K. pneumoniae in the mouse gut microbiome and drove bacterial populations to lose key virulence factors that act as phage receptors. Further, phage-mediated diversification of bacterial populations in the gut enabled co-evolution of phage variants with higher virulence and a broader host range. Altogether, the Klebsiella PhageBank represents a roadmap for both phage researchers and clinicians to enable phage therapy against a critical multidrug-resistant human pathogen.
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Project description:Klebsiella pneumoniae has risen to prominence as a major threat to human health, with hypervirulent and drug-resistant lineages spreading globally. Given their antimicrobial resistant phenotypes, new therapies are required for the treatment of these infections, and bacteriophages (phages) that kill Klebsiella are being identified for use in phage therapy. In order to circumvent the evolution of phage-resistance taking hold the way that drug-resistance has, clear and considered actions are needed in selecting the phages that would be used in therapeutic cocktails. It is known that annotation of phage genomes is poor, potentially obscuring those phages with the most therapeutic potential. Here we show that phages isolated from infrequently sampled environments have features of therapeutic potential and developed a computational tool called STEP3 to understand the evolutionary features that distinguish the component parts of diverse phages, features that proved particularly suitable to detection of virion proteins with only distantly related homologies. These features were integrated into an ensemble framework to achieve a stable and robust prediction performance by STEP3. Proteomics-based analysis of two phages validated the prediction accuracy of STEP3 and revealed the virions contain component parts that include DNA-binding factors, otherwise unrecognizable capsule degradation enzymes and membrane translocation factors.
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Project description:This SuperSeries is composed of the following subset Series: GSE35746: Comparative analysis of regulatory elements between Escherichia coli and Klebsiella pneumoniae by genome-wide transcription start site profiling [tiling arrays] GSE35821: Comparative analysis of regulatory elements between Escherichia coli and Klebsiella pneumoniae by genome-wide transcription start site profiling [TSS-Seq] Refer to individual Series
2012-07-29 | E-GEOD-35822 | biostudies-arrayexpress
Project description:Elucidating the RamA Regulon in Klebsiella pneumoniae and the transcriptome profiles of multidrug resistant Klebsiella pneumoniae
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Project description:We report the application of single-molecule-based sequencing technology for high-throughput profiling of transcription start sites for two enterobacteria: Escherichia coli and Klebsiella pneumoniae.By obtaining over fourteen billion bases of sequence from 5' RACE (rapid amplification of cDNA ends) followed by deep sequencing, we generated genome-wide TSS (transcription start site) maps for those two species. With experimentally derived TSS datasets, we examined usage of multiple TSSs, length of 5' UTR (untranslated region), SD (Shine-Dalgarno) sequence motif, promoter sequence motif, and dinucleotide preference near TSS site. In addition, we used the TSS datasets to identify sRNAs (small RNAs) in E. coli and K. pneumoniae. Based on these analysis, we compared regulatory elements including promoter, 5' UTR and sRNAs between two species, and investigated similarities and differences of upstream regulatory regions. Moreover, sRNAs were also compared and analyzed in terms of their sequences and target sequences, presenting possible working mechanisms of K. pneumoniae sRNAs by transferring prior knowledge from E. coli sRNAs. Examination of transcription start sites by biological duplicates from E. coli and K. pneumoniae
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Project description:To investigate the whole-genome gene expression difference between the wild-type and capsule deletion mutant in Klebsiella pneumoniae MGH 78578. The mutants analyzed in this study are further described in Huang T.W., Stapleton J.C., Chang H.Y., Tsai S.F., Palsson B.O., Charusanti P. Capsule removal via lambda-Red knockout system perturbs biofilm formation and fimbriae extression in Klesiella pneumoniae MGH 78578 (manuscript submission) A six chip study using total RNA recovered from three separate wild-type cultures and three separate cultures of a capsule deltion mutant of Klebsiella pneumoniae MGH 78578. The capsule gene cluster (KPN_02493 to KPN_02515) was entirely removed in the capsule deletion mutant. Each chip measures the expression level of 5,305 genes from Klebsiella pneumoniae MGH 78578 and the associated five plasmids (pKPN3, pKPN4, pKPN5, pKPN6 and pKPN7) with 50-mer oligo tiling array with 30-mer spacer.
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