Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1280179 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Horizontal gene transfer (HGT) is the major mechanism responsible for spread of antibiotic resistance. Antibiotic treatment has been suggested to promote HGT, either by directly affecting the conjugation process itself or by selecting for conjugations subsequent to DNA transfer. However, recent research suggests that the effect of antibiotic treatment on plasmid conjugation frequencies, and hence the spread of resistance plasmids, may have been overestimated. We addressed the question by quantifying transfer proteins and conjugation frequencies of a blaCTX-M-1 encoding IncI1 resistance plasmid in Escherichia coli MG1655 in the presence and absence of therapeutically relevant concentrations of cefotaxime (CTX). Analysis of the proteome by iTRAQ labeling and liquid chromatography tandem mass spectrometry revealed that Tra proteins were significantly up regulated in the presence of CTX. The up-regulation of the transfer machinery was confirmed at the transcriptional level for five selected genes. The CTX treatment did not cause induction of the SOS39 response as revealed by absence of significantly regulated SOS associated proteins in the proteome and no significant up-regulation of recA and sfiA genes. The frequency of plasmid conjugation, measured in an antibiotic free environment, increased significantly when the donor was pre-grown in broth containing CTX compared to growth without this drug, regardless of whether blaCTX-M-1 was located on the plasmid or in trans on the chromosome. The results shows that antibiotic treatment can affect expression of a plasmid conjugation machinery and subsequent DNA transfer.
2017-11-21 | PXD006679 | Pride
Project description:Plasmid fitness is directed by two orthogonal processes—vertical transfer through cell division and horizontal transfer through conjugation. When considered individually, improvements in either mode of transfer can promote how well a plasmid spreads and persists. Together, however, the metabolic cost of conjugation could create a tradeoff that constrains plasmid evolution. Here we present evidence for the presence, consequences, and molecular basis of a conjugation-growth tradeoff across 40 plasmids derived from clinical E. coli pathogens. We discover that most plasmids operate below a conjugation efficiency threshold for major growth effects, indicating strong natural selection for vertical transfer. Below this threshold, E. coli demonstrates a remarkable growth tolerance to over four orders of magnitude change in conjugation efficiency. This tolerance fades as nutrients become scarce and horizontal transfer attracts a greater share of host resources. Our results provide insight into evolutionary constraints directing plasmid fitness and strategies to combat the spread of antibiotic resistance.
2022-12-23 | GSE219270 | GEO
Project description:Plasmid conjugation is a key facilitator of horizontal gene transfer. Since plasmids often carry antibiotic resistance genes, they are crucial drivers of the world-wide rise of antibiotic resistance among pathogens. In natural, engineered and clinical environments, bacteria often grow in protective biofilms. Therefore, a better understanding of plasmid transfer in biofilms is needed. Our aim was to investigate plasmid transfer in a biofilm adapted wrinkly colony mutant of Xanthomonas retroflexus (XRw) with enhanced matrix production and reduced motility. We found that XRw biofilms had an increased uptake of the broad host-range IncP-1ϵ plasmid pKJK5 compared to the wild type. Proteomics revealed fewer flagellum associated proteins in XRw, suggesting that flagella were responsible for reducing plasmid uptake. This was confirmed by the higher plasmid uptake of non-flagellated ∆fliM mutants of X. retroflexus wild type and wrinkly mutant. Moreover, testing several flagella mutants of Pseudomonas putida suggested that the flagella effect was more general. We identified seven mechanisms with the potential to explain the flagella effect and simulated them in an individual-based model. Two mechanisms could thus be eliminated (increased distances between cells and increased lag times due to flagella). Another mechanism identified as viable in the modelling was eliminated by further experiments. Four additional proposed mechanisms have a reduced probability of plasmid transfer in common. Our findings highlight the important yet complex effects of flagella during bacterial conjugation in biofilms.
2024-01-26 | PXD040461 | Pride
Project description:Antibiotic resistance is exacerbated by the exchange of antibiotic resistance genes (ARGs) between microbes from diverse habitats. Plasmids are important ARGs mobile elements and are spread by horizontal gene transfer (HGT). In this study, we demonstrated the presence of multi-resistant plasmids from inhalable particulate matter (PM) and its effect on gene horizontal transfer. Three transferable multi-resistant plasmids were identified from PM in a hospital, using conjugative mating assays and nanopore sequencing. pTAir-3 contained 26 horizontal transfer elements and 10 ARGs. Importantly pTAir-5 harbored carbapenem resistance gene (blaOXA) which shows homology to plasmids from human and pig commensal bacteria, thus indicating that PM is a media for antibiotic resistant plasmid spread. In addition, 125 μg/mL PM2.5 and PM10 significantly increased the conjugative transfer rate by 110% and 30%, respectively, and augmented reactive oxygen species (ROS) levels. Underlying mechanisms were revealed by identifying the upregulated expressional levels of genes related to ROS, SOS, cell membranes, pilus generation, and transposition via genome-wide RNA sequencing. The study highlights the airborne spread of multi-resistant plasmids and the impact of inhalable PM on the horizontal transfer of antibiotic resistance.
2022-10-31 | GSE159850 | GEO
Project description:Causes lung, blood and wound infections
| PRJNA29549 | ENA
Project description:Staphylococcus aureus is responsible for a substantial number of invasive infections globally each year. These infections are problematic because they are frequently recalcitrant to antibiotic treatment. Antibiotic tolerance, the ability of bacteria to persist despite normally lethal doses of antibiotics, contributes to antibiotic treatment failure in S. aureus infections. To understand how antibiotic tolerance is induced, S. aureus biofilms exposed to multiple anti-staphylococcal antibiotics were examined using both quantitative proteomics and transposon sequencing. These screens indicated that arginine metabolism is involved in antibiotic tolerance within a biofilm and led to the hypothesis that depletion of arginine within S. aureus communities can induce antibiotic tolerance. Consistent with this hypothesis, inactivation of argH, the final gene in the arginine synthesis pathway, induces antibiotic tolerance. Arginine restriction was found to induce antibiotic tolerance via inhibition of protein synthesis. In a mouse skin infection model, an argH mutant has enhanced ability to survive antibiotic treatment with vancomycin, highlighting the relationship between arginine metabolism and antibiotic tolerance during S. aureus infection. Uncovering this link between arginine metabolism and antibiotic tolerance has the potential to open new therapeutic avenues targeting previously recalcitrant S. aureus infections.
2024-07-10 | GSE267626 | GEO
Project description:Kaiser2014 - Salmonella persistence after ciprofloxacin treatment
The model describes the bacterial tolerance to antibiotics. Using a mouse model for Salmonella diarrhea, the authors have found that bacterial persistence occurs in the presence of the antibiotic ciprofloxacin because Salmonella can exist in two different states. One, the fast-growing population that spreads in the host's tissues and the other, slow-growing "persister" population that hide out inside dendritic cells of the host's immune system and cannot be attacked by the antibiotics. However, this can be killed by adding agents that directly stimulate the host's immune defense.
This model is described in the article:
Cecum lymph node dendritic cells harbor slow-growing bacteria phenotypically tolerant to antibiotic treatment.
Kaiser P, Regoes RR, Dolowschiak T, Wotzka SY, Lengefeld J, Slack E, Grant AJ, Ackermann M, Hardt WD.
PLoS Biol. 2014 Feb 18;12(2):e1001793.
Abstract:
In vivo, antibiotics are often much less efficient than ex vivo and relapses can occur. The reasons for poor in vivo activity are still not completely understood. We have studied the fluoroquinolone antibiotic ciprofloxacin in an animal model for complicated Salmonellosis. High-dose ciprofloxacin treatment efficiently reduced pathogen loads in feces and most organs. However, the cecum draining lymph node (cLN), the gut tissue, and the spleen retained surviving bacteria. In cLN, approximately 10%-20% of the bacteria remained viable. These phenotypically tolerant bacteria lodged mostly within CD103⁺CX₃CR1⁻CD11c⁺ dendritic cells, remained genetically susceptible to ciprofloxacin, were sufficient to reinitiate infection after the end of the therapy, and displayed an extremely slow growth rate, as shown by mathematical analysis of infections with mixed inocula and segregative plasmid experiments. The slow growth was sufficient to explain recalcitrance to antibiotics treatment. Therefore, slow-growing antibiotic-tolerant bacteria lodged within dendritic cells can explain poor in vivo antibiotic activity and relapse. Administration of LPS or CpG, known elicitors of innate immune defense, reduced the loads of tolerant bacteria. Thus, manipulating innate immunity may augment the in vivo activity of antibiotics.
This model is hosted on BioModels Database and identified
by: MODEL1312170001.
To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource
for published quantitative kinetic models.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to the public
domain worldwide. Please refer to CC0 Public Domain
Dedication for more information.
2024-09-02 | BIOMD0000000527 | BioModels
Project description:Pseudomonas aeruginosa evolving in the cystic fibrosis (CF) lung encounters selection via iron-limitation, antibiotics, immune system effectors and other microbes. Standing genetic variation, which depends on rates of horizontal gene transfer (HGT) and mutation supply, controls response to challenges. HGT may increase if new clones successfully invade, while mutator strains increase new mutations. We sought to ascertain genomic signatures of invasion and whether, in the absence of novel invasion, mutator-containing P. aeruginosa populations from chronically infected CF lung are more genetically variable than nonmutator populations. Forty-nine strains from 14 patients treated over three years at Necker Children’s Hospital in Paris were phenotyped for antibiotic resistance, mucoidy and mutator status, and then genotyped by rep-PCR, PFGE and MLST analysis. Overall, strains exhibited greater genetic similarity within patients than among patients, with initial and terminal clones differing markedly between series, indicating unrelated clones independently established infections and resisted invasions that might enlarge genetic variation by sexual recombination. Mutator series were more likely to be multiply antibiotic-resistant, but were no more genetically variable at the single nucleotide level. DNA microarray analyses of bacterial genomes in two longitudinal series of equal duration, one containing and one lacking mutators, revealed both series conspicuously lack genes encoding proteins involved in attachment, motility and amino acid biosynthesis. The mutator series also contained fewer genes hybridizing to canonical PAO1 genome sequences. These data suggest genetic variation arising from mutators may be limited in scope, transient in nature or not easily resolved by fingerprinting, MLST or comparative genomic analyses. Clinical P. aeruginosa hypermutator and nonhypermutator lineages from CF lung. Array-based genome hybridization.
2011-10-31 | E-GEOD-25481 | biostudies-arrayexpress