Ontology highlight
ABSTRACT:
PROVIDER: PRJNA842005 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR19400573_1.fastq.gz | Fastqsanger.gz | |||
| SRR19400573_2.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:RNA sequencing (RNA-seq) of phage infected bacterial cultures offers a snapshot of transcriptional events occurring during the infection process, providing insights into the phage transcriptional organization as well as the bacterial response. To better mimic real environmental contexts, we performed RNA-seq of P. aeruginosa PAO1 cultures infected with phage LUZ19 in a mammalian cell culture medium (MCCM) to better simulate a phage therapy event, and the data were compared to LB medium. Regardless of the media, phage LUZ19 induces significant transcriptional changes in the bacterial host over time, particularly during early infection (t= 5 min) and gradually shuts down bacterial transcription. In a common response in both media, 56 P. aeruginosa PAO1 genes are differentially transcribed and clustered into several functional categories such as metabolism, translation and transcription. Our data allowed us to tease apart a medium-specific response during infection from the identified infection-associated responses. This reinforces the concept that phages overtake bacterial transcriptome in a strict manner to gain control of the bacterial machinery and reallocate resources for infection, in this case overcoming the nutritional limitations of the mammalian cell culture medium. From a phage therapy perspective, this study contributes towards a better understanding of phage-host interaction in human physiological conditions and demonstrates the versatility of phage LUZ19 to adapt to different environments.
2020-11-28 | GSE162278 | GEO
Project description:Phage therapy is a therapeutic approach to treat multidrug resistant infections that employs lytic bacteriophages (phages) to eliminate bacteria. Despite the abundant evidence for its success as an antimicrobial in Eastern Europe, there is scarce data regarding its effects on the human host. Here, we aimed to understand how lytic phages interact with cells of the airway epithelium, the tissue site that is colonized by bacterial biofilms in numerous chronic respiratory disorders. Using a panel of Pseudomonas aeruginosa phages and human airway epithelial cells derived from a person with cystic fibrosis, we determined that interactions between phages and epithelial cells depend on specific phage properties as well as physiochemical features of the microenvironment. Although poor at internalizing phages, the airway epithelium responds to phage exposure by changing its transcriptional profile and secreting antiviral and proinflammatory cytokines that correlate with specific phage families. Overall, our findings indicate that mammalian responses to phages are heterogenous and could potentially alter the way that respiratory local defenses aid in bacterial clearance during phage therapy. Thus, besides phage receptor specificity in a particular bacterial isolate, the criteria to select lytic phages for therapy should be expanded to include mammalian cell responses.
2024-02-19 | GSE255619 | GEO
Project description:Phage therapy is a promising adjunct therapeutic approach against bacterial multidrug-resistant infections, including Pseudomonas aeruginosa-derived infections. Nevertheless, the current knowledge about the phage-bacteria interaction within a human environment is limited. In this work, we performed a transcriptome analysis of phage-infected P. aeruginosa adhered to a human epithelium (Nuli-1 ATCC® CRL-4011™). To this end, we performed RNA-sequencing from a complex mixture comprising phage–bacteria–human cells at early, middle, and late infection and compared it to uninfected adhered bacteria. Overall, we demonstrated that phage genome transcription is unaltered by bacterial growth and phage employs a core strategy of predation through upregulation of prophage-associated genes, a shutdown of bacterial surface receptors, and motility inhibition. In addition, specific responses were captured under lung-simulating conditions, with the expression of genes related to spermidine syntheses, sulfate acquisition, spermidine syntheses, biofilm formation (both alginate and polysaccharide syntheses), lipopolysaccharide (LPS) modification, pyochelin expression, and downregulation of virulence regulators. These responses should be carefully studied in detail to better discern phage-induced changes from bacterial responses against phage. Our results establish the relevance of using complex settings that mimics in vivo conditions to study phage-bacteria interplay, being obvious the phage versatility on bacterial cell invasion.
2023-05-31 | GSE213159 | 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: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: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.
2024-10-01 | GSE272297 | GEO
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:We analyzed RNA-Seq data of two Staphylococcus aureus strains, Newman and SH1000, infected by Kayvirus phage K. Staphylococcus virus K is used in the phage therapy, its genome is 148 kb long consisting of dsDNA with long terminal repeats, and encodes 233 ORFs and 4 tRNAs. The sampling times 0, 2, 5, 10, 20, and 30 minutes after infection were chosen based on the growth characteristics of the phage K at the two S. aureus strains. From the RNA-Seq data we determined transcriptional profile of the phage K and its hosts, which allowed us to identify differentially expressed genes, ncRNAs, and promotor and terminator sites. Transcription of the phage K genes starts immediately after the infection of bacterial cells and we found a gradual take-over by phage K transcripts in the infected cells. The temporal transcriptional profile of phage K was similar in both strains and the relative expression of phage K genes shows three distinct transcript types – early, middle, and late based on the time they reach maximum expression. The bacterial response to phage K infection is similar to the general stress response. It includes the upregulation of nucleotide, amino acid and energy synthesis and transporter genes and the downregulation of transcription factors. The expression of particular virulence genes involved in adhesion and immune system evasion as well as prophage integrases were marginally affected. This work unveils the versatile nature of phage K infection leading to its broad host range
2022-03-23 | GSE190637 | GEO