Ontology highlight
ABSTRACT:
PROVIDER: PRJNA884199 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR21707775.fastq.gz | Fastqsanger.gz | |||
| SRR21707776.fastq.gz | Fastqsanger.gz | |||
| SRR21707777.fastq.gz | Fastqsanger.gz | |||
| SRR21707778.fastq.gz | Fastqsanger.gz | |||
| SRR21707779.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 11 |
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Project description:Transcription factors play a key role in the development of a number of cancers, and therapeutically targeting them has remained a challenge. In prostate cancer, the ETS transcription factor ERG is recurrently rearranged and likely plays a critical role in prostate oncogenesis. Here we identified a series of peptides from a phage-display library that interact specifically with the DNA binding domain of ERG. The interactive interface was mapped to 9-residues in the 3rd helix of the ETS domain that is critical for ERG transcriptional activity. The peptides were found to efficiently disrupt ERG-mediated protein-protein interactions, transcription, DNA damage, and cell invasion, as well as attenuate ERG recruitment to target gene loci. Furthermore, a retroinverso peptidomimetic version of the peptide sequence suppressed tumor growth, intravasation, and metastasis in vivo. Taken together, our results demonstrate that transcription factors have specific residues important for protein-protein interactions and disrupting those critical interactions may be an effective therapeutic strategy. Examination of ERG in VCaP cells with respect to peptidomimetics treatment
2014-07-15 | E-GEOD-58939 | biostudies-arrayexpress
Project description:Clinical case studies have reported that the combined use of specific lytic phage(s) and antibiotics reduces the severity of difficult-to-treat Pseudomonas aeruginosa infections in many patients. In vitro methods that attempt to reproduce specific pathophysiological conditions can provide a reliable assessment of the antibacterial effects of phages. Here, we measured bacterial killing kinetics and individual phage replication in different growth phases, including biofilms, elucidating factors influencing the efficacy of two phages against the laboratory strain P. aeruginosa PAO1. While two-phage combination treatment effectively eliminated P. aeruginosa in routine broth and in infected human lung cell cultures, the emergence of phage-resistant variants occurred under both conditions. Phage combination displayed initial inhibition of biofilm dispersal, but sustained control was achieved only with a combination of phages and meropenem. In contrast, surface-attached biofilm exhibited tolerance to phage and/or meropenem, suggesting a spatiotemporal variation in antibacterial effect. Moreover, the phage with the shorter lysis time killed P. aeruginosa more rapidly, selecting a specific nucleotide polymorphism that likely conferred a competitive disadvantage and cross resistance to the second phage of the combination. These findings highlight biofilm developmental phase, inter-phage competition and phage resistance as factors limiting the in vitro efficacy of a phage combination. However, their precise impact on the outcome of phage therapy remains uncertain, necessitating validation through phage efficacy trials in order to establish clearer correlations between laboratory assessments and clinical results.
2024-07-17 | GSE271537 | GEO
Project description:The emergence of carbapenem-resistant Acinetobacter baumannii has been increasingly reported, leading to more challenges in treating its infections. With the development of phage therapy and phage-antibiotic combinations, it is possible to improve the treatment of bacterial infections. In the present study, a vB_AbaP_WU2001 (vWU2001 for short) phage-specific CRAB was isolated and the genome size is 40,792 bp in length. The novel phage vWU2001 belongs to the Autographiviridae family and the order Caudovirales. Shotgun proteomics identified 289 proteins. The broad host range phage vWU2001 displayed a high adsorption rate, short latent period, large burst size and good stability. The phage could reduce preformed biofilms and inhibit biofilm formation. The combination of phage vWU2001 and colistin had significantly higher bacterial growth inhibition activity than that of phage, or colistin alone. The efficacy of the combined treatment was also evaluated in Galleria mellonella. The evaluation of its therapeutic potential revealed that the combination of phage and colistin showed a significantly greater increase in G. mellonella survival and clearance of bacterial number compared to that of phage or colistin alone, indicating that the combination was synergistic against CRAB. The results demonstrated that phage vWU2001 has the potential to be developed as an antibacterial agent.
2021-09-04 | PXD028206 | JPOST Repository
Project description:The present work describes LC-ESI-MS/MS analyses of tryptic digestion peptides from phages that infect Staphylococcus aureus-causing mastitis, and isolated from dairy products. A total of 1935 non-redundant peptides belonging to 1282 proteins were identified and analyzed. Among them, 80 staphylococcal peptides from phages were confirmed. These peptides belong to proteins such as phage repressors, structural phage proteins, uncharacterized phage proteins and complement inhibitors. Moreover, of the phage origin peptides found, eighteen of them were specific to S. aureus strains. These diagnostic peptides could be useful for the identification and characterization of S. aureus strains that cause mastitis. Furthermore, a study of bacteriophage phylogeny and the relationship among the identified phage peptides and the bacteria they infect was also performed. The results show the specific peptides which are present in closely related phages, and the existing links between bacteriophage phylogeny and the respective Staphylococcus spp. infected.
2021-03-25 | PXD023530 | Pride
Project description:Purified phage was used to prevent tumor growth in a mouse model of bacteria aggravated-colorectal cancer. Composite E. coli phage or vehicle control was added to the drinking water of specific pathogen free (SPF) APCmin mice and animals were colonized with E.coli NC101. APCmin mice displayed no overall difference in the number of tumors that formed within the small intestine, however colonization with E. coli NC101 accelerated the growth of tumors resulting in a significant increase in large tumor formation. Importantly, bacteriophage treatment of AIEC colonized APCmin animals significantly reduced E. coli colonization.
2019-03-01 | GSE124123 | GEO
Project description:Transcription factors play a key role in the development of a number of cancers, and therapeutically targeting them has remained a challenge. In prostate cancer, the ETS transcription factor ERG is recurrently rearranged and likely plays a critical role in prostate oncogenesis. Here we identified a series of peptides from a phage-display library that interact specifically with the DNA binding domain of ERG. The interactive interface was mapped to 9-residues in the 3rd helix of the ETS domain that is critical for ERG transcriptional activity. The peptides were found to efficiently disrupt ERG-mediated protein-protein interactions, transcription, DNA damage, and cell invasion, as well as attenuate ERG recruitment to target gene loci. Furthermore, a retroinverso peptidomimetic version of the peptide sequence suppressed tumor growth, intravasation, and metastasis in vivo. Taken together, our results demonstrate that transcription factors have specific residues important for protein-protein interactions and disrupting those critical interactions may be an effective therapeutic strategy.
2014-07-15 | GSE58939 | GEO
Project description:An important lesson from the war on pathogenic bacteria has been the need to understand the physiological responses and evolution of natural microbial communities. Bacterial populations in the environment are generally forming biofilms subject to some level of phage predation. These multicellular communities are notoriously resistant to antimicrobials and, consequently, very difficult to eradicate. This has sparked the search for new therapeutic alternatives, including phage therapy. This study demonstrates that S. aureus biofilms formed in the presence of a non-lethal dose of phage phiIPLA-RODI exhibit a unique physiological state that could potentially benefit both the host and the predator. Thus, biofilms formed under phage pressure are thicker and have a greater DNA content. Also, the virus-infected biofilm displayed major transcriptional differences compared to an untreated control. Significantly, RNA-seq data revealed activation of the stringent response, which could slow down the advance of the bacteriophage within the biofilm. The end result would be an equilibrium that would help bacterial cells to withstand environmental challenges, while maintaining a reservoir of sensitive bacterial cells available to the phage upon reactivation of the dormant carrier population.
2017-01-20 | GSE87706 | GEO
Project description:We developed a surface-displayed library of 117 human antimicrobial peptides (AMPs) and over 3000 human AMP variants in a laboratory E. coli strain expressing PhoP and PhoQ from Salmonella Typhimurium. We used sort-seq (fluorescence-activated cell sorting followed by next-generation sequencing) to characterize PhoPQ activation by these surface-displayed AMPs.
2022-11-09 | GSE174191 | GEO