Extensive antimicrobial resistance mobilization via multicopy plasmid encapsidation mediated by temperate phages
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PROVIDER: PRJEB35069 | ENA |
REPOSITORIES: ENA
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Project description:ObjectivesTo investigate the relevance of multicopy plasmids in antimicrobial resistance and assess their mobilization mediated by phage particles.MethodsSeveral databases with complete sequences of plasmids and annotated genes were analysed. The 16S methyltransferase gene armA conferring high-level aminoglycoside resistance was used as a marker in eight different plasmids, from different incompatibility groups, and with differing sizes and plasmid copy numbers. All plasmids were transformed into Escherichia coli bearing one of four different lysogenic phages. Upon induction, encapsidation of armA in phage particles was evaluated using qRT-PCR and Southern blotting.ResultsMulticopy plasmids carry a vast set of emerging clinically important antimicrobial resistance genes. However, 60% of these plasmids do not bear mobility (MOB) genes. When carried on these multicopy plasmids, mobilization of a marker gene armA into phage capsids was up to 10000 times more frequent than when it was encoded by a large plasmid with a low copy number.ConclusionsMulticopy plasmids and phages, two major mobile genetic elements (MGE) in bacteria, represent a novel high-efficiency transmission route of antimicrobial resistance genes that deserves further investigation.
| S-EPMC7566468 | biostudies-literature
Project description:Modern sequencing technologies have provided insight into the genetic diversity of numerous species, including the human pathogen Pseudomonas aeruginosa. Bacterial genomes often harbor bacteriophage genomes (prophages), which can account for upwards of 20% of the genome. Prior studies have found P. aeruginosa prophages that contribute to their host's pathogenicity and fitness. These advantages come in many different forms, including the production of toxins, promotion of biofilm formation, and displacement of other P. aeruginosa strains. While several different genera and species of P. aeruginosa prophages have been studied, there has not been a comprehensive study of the overall diversity of P. aeruginosa-infecting prophages. Here, we present the results of just such an analysis. A total of 6,852 high-confidence prophages were identified from 5,383 P. aeruginosa genomes from strains isolated from the human body and other environments. In total, 3,201 unique prophage sequences were identified. While 53.1% of these prophage sequences displayed sequence similarity to publicly available phage genomes, novel and highly mosaic prophages were discovered. Among these prophages, there is extensive diversity, including diversity within the functionally conserved integrase and C repressor coding regions, two genes responsible for prophage entering and persisting through the lysogenic life cycle. Analysis of integrase, C repressor, and terminase coding regions revealed extensive reassortment among P. aeruginosa prophages. This catalog of P. aeruginosa prophages provides a resource for future studies into the evolution of the species. IMPORTANCE Prophages play a critical role in the evolution of their host species and can also contribute to the virulence and fitness of pathogenic species. Here, we conducted a comprehensive investigation of prophage sequences from 5,383 publicly available Pseudomonas aeruginosa genomes from human as well as environmental isolates. We identified a diverse population of prophages, including tailed phages, inoviruses, and microviruses; 46.9% of the prophage sequences found share no significant sequence similarity with characterized phages, representing a vast array of novel P. aeruginosa-infecting phages. Our investigation into these prophages found substantial evidence of reassortment. In producing this, the first catalog of P. aeruginosa prophages, we uncovered both novel prophages as well as genetic content that have yet to be explored.
| S-EPMC8865926 | biostudies-literature
Project description:Successful gene therapy for β-thalassemia requires optimal numbers of autologous gene-transduced hematopoietic progenitors stem cells (HPSC) with high repopulating capacity and mobilization is the optimal approach for achieving this goal. We performed a clinical study to investigate safety and efficacy of G-CSF+AMD3100 mobilization in four adult with β-thalassemia to reach a cell dose of â¥8x106 CD34+cells/Kg and to characterize the CD34+cell populations mobilized before and after plerixafor administration. The procedure resulted well-tolerated in all patients. Three of the four patients reached the target cell dose or more in single-apheresis collections, even one patient where a significant dose reduction of G-CSF was imposed due to early hyperleukocytosis. A significant increase in the number of circulating CD34+ cells/µl (12.1± 8.2 fold), and in the frequency of the more primitive CD34+/CD133+/CD38- cells (1.7±0.7 fold) was unanimously observed after AMD3100 addiction. Intraindividual comparison of gene expression profile of CD34+ cells mobilized with G-CSF versus G-CSF+ AMD3100 highlighted a different expression pattern of genes involved in the processes of HSC/stroma adhesion, homing, cell motility and transcription regulation. Overall, the safety profile, the yield, and the expression of genes that potentially promote superior engraftment depict G-CSF+AMD3100 mobilized HSC as optimal graft source for β-thalassemia gene therapy One experiment performed on purified CD34+ PBPC of the same patient 1 after mobilization with G-CSF + Plerixafor , and after mobilization with G-CSF alone. Universal Human Reference RNA (Stratagene, La Jolla, CA), was used as reference.
2017-04-28 | E-GEOD-70219 | biostudies-arrayexpress
Project description:Bacterial mobilization of organically bound sulfur in the mycorrhizosphere to improve plant sulfur supply
| PRJEB37537 | ENA
Project description:Multicopy plasmids allow bacteria to escape from fitness trade-offs during evolutionary innovation
| PRJEB25055 | ENA
Project description:Lipid mobilization (lipolysis) in white adipose tissue (WAT) critically controls lipid turnover and adiposity in humans. While the acute regulation of lipolysis has been studied in detail, the transcriptional determinants of WAT lipolytic activity remain still largely unexplored. Here we show that the genetic inactivation of transcriptional co-factor transducin beta-like-related (TBLR) 1 blunts the lipolytic response of white adipocytes through the impairment of cAMP-dependent signal transduction. Indeed, mice lacking TBLR1 in adipocytes are defective in fasting-induced lipid mobilization and when placed on a high fat diet show aggravated adiposity, glucose intolerance and insulin resistance. TBLR1 levels are found to increase under lipolytic conditions in WAT of both human patients and mice, correlating with serum free fatty acids (FFA). As a critical regulator of WAT cAMP signaling and lipid mobilization, proper activity of TBLR1 in adipocytes may thus represent a critical molecular checkpoint for the prevention of metabolic dysfunction in subjects with obesity-related disorders. We used microarrays to identify global gene expression in 3T3-L1 adipocytes lacking TBLR1 and compared gene expression to control shRNA treated cells in both basal and isoproterenol stimulated states. We analyzed 12 RNA samples extracted from 3T3-L1 adipocytes that were treated with either control or TBLR1 specific shRNAs and with or without 10 µM isoproterenol for 3 hrs. Three replicates of each condition.
2013-04-01 | E-GEOD-43658 | biostudies-arrayexpress
Project description:Nociceptive nerves regulate haematopoietic stem cell mobilization
| PRJNA657999 | ENA
Project description:The Liverpool Epidemic Strain (LES) is a polylysogenic, transmissible strain of Pseudomonas aeruginosa, capable of superinfecting existing P. aeruginosa respiratory infections in individuals with cystic fibrosis (CF). The LES phages are highly active in the CF lung and may have a role in the competitiveness of the LES in vivo. In this study, we tested this by competing isogenic PAO1 strains that differed only by the presence or absence of LES prophages in a rat model of chronic lung infection. Lysogens invaded phage-susceptible populations, both in head-to-head competition and when invading from rare, in the spatially structured, heterogeneous lung environment. Appreciable densities of free phages in lung tissue confirmed active phage lysis in vivo. Moreover, we observed lysogenic conversion of the phage-susceptible competitor. These results suggest that temperate phages may have an important role in the competitiveness of the LES in chronic lung infection by acting as anti-competitor weapons.
| S-EPMC4950967 | biostudies-literature
Project description:Microbial communities are accompanied by a diverse array of viruses. Through infections of abundant microbes, these viruses have the potential to mediate competition within the community, effectively weakening competitive interactions and promoting coexistence. This is of particular relevance for host-associated microbial communities, because the diversity of the microbiota has been linked to host health and functioning. Here, we study the interaction between two key members of the microbiota of the freshwater metazoan Hydra vulgaris The two commensal bacteria Curvibacter sp. and Duganella sp. protect their host from fungal infections, but only if both of them are present. Coexistence of the two bacteria is thus beneficial for Hydra Intriguingly, Duganella sp. appears to be the superior competitor in vitro due to its higher growth rate when both bacteria are grown separately, but in co-culture the outcome of competition depends on the relative initial abundances of the two species. The presence of an inducible prophage in the Curvibacter sp. genome, which is able to lytically infect Duganella sp., led us to hypothesize that the phage modulates the interaction between these two key members of the Hydra microbiota. Using a mathematical model, we show that the interplay of the lysogenic life cycle of the Curvibacter phage and the lytic life cycle on Duganella sp. can explain the observed complex competitive interaction between the two bacteria. Our results highlight the importance of taking lysogeny into account for understanding microbe-virus interactions and show the complex role phages can play in promoting coexistence of their bacterial hosts.
| S-EPMC5746566 | biostudies-literature
Project description: Not available
| S-EPMC10688831 | biostudies-literature