Targeted phage hunting in clinical isolates
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB68301 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR12251639_1.fastq.gz | Fastqsanger.gz | |||
| ERR12251639_2.fastq.gz | Fastqsanger.gz | |||
| ERR12251640_1.fastq.gz | Fastqsanger.gz | |||
| ERR12251640_2.fastq.gz | Fastqsanger.gz | |||
| ERR12251641_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 18 |
Similar Datasets
Project description:hvKP ATCC43816 and its lytic phage H5 were employed as a phage-antibiotic combination model. Based on the comprehensive characterization of phages, including cryo-electron microscopy, we evaluated the synergic effect of H5 on bacterial killing in vitro when combined with multiple antibiotics, and analyzed the advantages of phage-antibiotic combinations from an evolutionary perspective and proposes a novel PAS mechanism by using ceftazidime as an example.
2023-09-14 | GSE237490 | GEO
Project description:Salmonella enterica serovar Typhimurium (S. Typhimurium) definitive phage type 104 (DT104) has caused significant morbidity and mortality in humans and animals for almost three decades. We have completed the full DNA sequence of one DT104 strain, NCTC13348 and show that the main differences between the genome of this isolate and the previously sequenced S. Typhimurium LT2 lie in integrated prophage elements and the Salmonella Genomic Island 1 encoding antibiotic resistance genes. Thirteen isolates of S. Typhimurium DT104 with different pulsed field gel electrophoresis (PFGE) profiles were analyzed by multi locus sequence typing (MLST), plasmid profiling, hybridization to a Pan-Salmonella DNA microarray and prophage-based multiplex PCR. All the isolates belonged to a single MLST type ST19. Microarray data demonstrated that the 13 DT104 isolates were remarkably conserved in gene content. The PFGE band-size differences in these isolates could be explained to a great extent by changes in prophage and plasmid content. Thus, here the nature of variation in different S. Typhimurium DT104 isolates is further defined at the genome level illustrating how this phage type is evolving over time.
2008-09-05 | E-MTAB-20 | biostudies-arrayexpress
Project description:Virulent bacteriophages (or phages) are viruses that specifically infect and lyse a bacterial host. When multiple phages co-infect a bacterial host, the extent of lysis, dynamics of bacteria-phage and phage-phage interactions are expected to vary. The objective of this study is to identify the factors influencing the interaction of two virulent phages with different Pseudomonas aeruginosa growth states (planktonic, an infected epithelial cell line, and biofilm) by measuring the bacterial time-kill and individual phage replication kinetics. A single administration of phages effectively reduced P. aeruginosa viability in planktonic conditions and infected human lung cell cultures, but phage-resistant variants subsequently emerged. In static biofilms, the phage combination displayed initial inhibition of biofilm dispersal, but sustained control was achieved only by combining phages and meropenem antibiotic. In contrast, adherent biofilms showed tolerance to phage and/or meropenem, suggesting a spatiotemporal variation in the phage-bacterial interaction. The kinetics of adsorption of each phage to P. aeruginosa during single- or co-administration were comparable. However, the phage with the shorter lysis time depleted bacterial resources early and selected a specific nucleotide polymorphism that conferred a competitive disadvantage and cross-resistance to the second phage. The extent and strength of this phage-phage competition and genetic loci conferring phage resistance, are, however, P. aeruginosa genotype dependent. Nevertheless, adding phages sequentially resulted in their unimpeded replication with no significant increase in bacterial host lysis. These results highlight the interrelatedness of phage-phage competition, phage resistance and specific bacterial growth state (planktonic/biofilm) in shaping the interplay among P. aeruginosa and virulent phages.
2024-07-17 | GSE271537 | GEO
Project description:Klebsiella pneumoniae is one of the most threatening multi-drug-resistant pathogens today, with phage therapy being a promising alternative for personalized treatments. However, the intrinsic capsule diversity in Klebsiella spp. poses a substantial barrier to the phage host range, complicating the development of broad-spectrum phage-based treatments. Here, we have isolated and genomically characterized phages capable of infecting each of the acquired 77 reference serotypes of Klebsiella spp., including capsular types widespread among high-risk K. pneumoniae clones causing nosocomial infections. We demonstrated the possibility of isolating phages for all capsular types in the collection, revealing high capsular specificity among taxonomically related phages, in contrast to a few phages that exhibited broad-spectrum infection capabilities. To decipher the determinants of the specificity of these phages, we focused on their receptor-binding proteins, with particular attention to depolymerases. We also explored the possibility of designing a broad-spectrum phage cocktail based on phages isolated in reference capsular-type strains and determining the ability to lyse relevant clinical isolates. A combination of 12 phages capable of infecting 55% of the reference Klebsiella spp. serotypes was tested on a panel of carbapenem-resistant K. pneumoniae clinical isolates. Thirty-one percent of isolates were susceptible to the phage cocktail. However, our results suggest that in a highly variable encapsulated bacterial host, phage hunting must be directed to the specific Klebsiella isolates. This work is a step forward in the understanding of the complexity of phage-host interactions and highlights the importance of implementing precise and phage-specific strategies to treat K. pneumoniae infections worldwide.IMPORTANCEThe emergence of resistant bacteria is a serious global health problem. In the absence of effective treatments, phages are a personalized and effective therapeutic alternative. However, little is still known about phage-host interactions, which are key to implementing effective strategies. Here, we focus on the study of Klebsiella pneumoniae, a highly pathogenic encapsulated bacterium. The complexity and variability of the capsule, where in most cases phage receptors are found, make it difficult for phage-based treatments. Here, we isolated a large collection of Klebsiella phages against all the reference strains and in a cohort of clinical isolates. Our results suggest that clinical isolates represent a challenge, especially high-risk clones. Thus, we propose targeted phage hunting as an effective strategy to implement phage-derived therapies. Our results are a step forward for new phage-based strategies to control K. pneumoniae infections, highlighting the importance of understanding phage-host interactions to design personalized treatments against Klebsiella spp.
| S-EPMC11448410 | biostudies-literature
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:Rapidly growing antibiotic resistance among gastrointestinal pathogens, and the ability of antibiotics to induce the virulence of these pathogens makes it increasingly difficult to rely on antibiotics to treat gastrointestinal infections. The probiotic E. coli strain Nissle 1917 (EcN) is the active component of the pharmaceutical preparation Mutaflor® and has been successfully used in the treatment of gastrointestinal disorders. Gut bacteriophages are dominant players in maintaining the microbial homeostasis in the gut, however, their interaction with incoming probiotic bacteria remains to be at conception. The presence of bacteriophages in the gut makes it inevitable for any probiotic bacteria to be phage resistant, in order to survive and successfully colonize the gut. This study addresses the phage resistance of EcN, specifically against lytic T4 phage infection. From various experiments we could show that i) EcN is resistant towards T4 phage infection, ii) EcN’s K5 polysaccharide capsule plays a crucial role in T4 phage resistance and iii) EcN’s lipopolysaccharide (LPS) inactivates T4 phages and notably, treatment with the antibiotic polymyxin B which neutralizes the LPS destroyed the phage inactivation ability of isolated LPS from EcN. Our results further indicate that N-acetylglucosamine at the distal end of O6 antigen in EcN’s LPS could be the interacting partner with T4 phages. From our findings, we have reported for the first time, the role of EcN’s K5 capsule and LPS in its defense against T4 phages. In addition, by inactivating the T4 phages, EcN also protects E. coli K-12 strains from phage infection in tri-culture experiments. The combination of the identified properties is not found in other tested commensal E. coli strains. Furthermore, our research highlights phage resistance as an additional safety feature of EcN, a clinically successful probiotic E. coli strain.
2019-08-27 | GSE135946 | GEO
Project description:Multiple immune pathways in humans conjugate ubiquitin-like proteins to virus and host molecules as a means of antiviral defense. Here we studied an anti-phage defense system in bacteria, comprising a ubiquitin-like protein, ubiquitin-conjugating enzymes E1 and E2, and a deubiquitinase. We show that during phage infection, this system specifically conjugates the ubiquitin-like protein to the phage central tail fiber, a protein at the tip of the tail that is essential for tail assembly as well as for recognition of the target host receptor. Following infection, cells encoding this defense system release a mixture of partially assembled, tailless phage particles, and fully assembled phages in which the central tail fiber is obstructed by the covalently attached ubiquitin-like protein. These phages exhibit severely impaired infectivity, explaining how the defense system protects the bacterial population from the spread of phage infection. Our findings demonstrate that conjugation of ubiquitin-like proteins is an antiviral strategy conserved across the tree of life.
2024-05-08 | GSE262579 | GEO
Project description:Quorum sensing (QS) is the cell density-dependent virulence factor regulator in Pseudomonas aeruginosa. Here, we elucidate PIT2, a phage-encoded inhibitor of the QS regulator LasR, derived from the lytic Pseudomonas phage LMA2. PIT2 inhibits the effectors PrpL and LasA of the type 2 secretion system of P. aeruginosa and attenuates bacterial virulence towards HeLa cells and in Galleria mellonella. Using RNAseq-based differential gene expression analysis, the effect of PIT2 on the LasR regulatory network was revealed. Moreover, the specific interaction between LasR and PIT2 was determined. These data expand our knowledge on phage-encoded modulators of the bacterial metabolism, as this examples an anti-virulence protein derived from a lytic phage. From an applied perspective, this phage protein reveals and exploits an interesting anti-virulence target in P. aeruginosa. As such, it lays the foundation for a new phage-inspired anti-virulence strategy to combat multidrug resistant pathogens and opens the door for SynBio applications.
2023-09-27 | GSE227677 | GEO
Project description:Genomic material isolated from purified phage YerA41 lysate was shown to contain RNA. YerA41 phage lysate was RNase treated to remove phage-external RNA and total RNA was then isolated from the phage preparate using Qiagen Rneasy mini kit. The isolated RNA was sequenced to elucidate its origin. The results suggested that the RNA originated from intact ribosomes of the host bacterium that contaminated the phage lysate.
2022-04-04 | GSE199969 | GEO