Staphylococcus aureus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA320874 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR8592690_1.fastq.gz | Fastqsanger.gz | |||
| SRR8592690_2.fastq.gz | Fastqsanger.gz | |||
| SRR8592700_1.fastq.gz | Fastqsanger.gz | |||
| SRR8592700_2.fastq.gz | Fastqsanger.gz | |||
| SRR8592681_1.fastq.gz | Fastqsanger.gz |
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Project description:The rise of antibiotic resistance in many bacterial pathogens has been driven by the spread of a few successful strains, suggesting that some bacteria are genetically pre-disposed to evolving resistance. We tested this hypothesis by challenging a diverse set of 222 strains of Staphylococcus aureus with the antibiotic ciprofloxacin in a large-scale evolution experiment. Surprisingly, we found that a single efflux pump, norA, causes widespread variation in evolvability across the diversity of S. aureus. In most lineages of S. aureus, elevated norA expression potentiated evolution by increasing the fitness benefit provided by resistance mutations in DNA topoisomerase under ciprofloxacin treatment. Amplification of norA provided a further mechanism of rapid evolution, but this was restricted to strains from CC398. Crucially, chemically inhibiting NorA effectively prevented the evolution of resistance across the diversity of S. aureus. Our study shows that the underlying genetic diversity of pathogenic bacteria plays a key role in shaping resistance evolution. Understanding this link makes it possible to predict which strains are likely to evolve resistance and to optimize inhibitor use to prevent this outcome.
2020-07-05 | GSE150762 | GEO
Project description:<p>While bacterial metabolism is known to impact antibiotic efficacy and virulence, the metabolic capacities of individual microbes in cystic fibrosis lung infections are difficult to disentangle from sputum samples. Here, we show that untargeted metabolomic profiling of supernatants of multiple strains of<em> Pseudomonas aeruginosa</em> and <em>Staphylococcus aureus </em>grown in monoculture in synthetic cystic fibrosis media (SCFM) reveal distinct species-specific metabolic signatures with limited strain-to-strain variability. The majority of metabolites significantly consumed by <em>S. aureus </em>were also consumed by <em>P. aeruginosa</em>, indicating that <em>P. aeruginosa</em> has the flexibility to metabolically outcompete<em> S. aureus </em>in coculture even in the absence of other pathogen-pathogen interactions. Finally, metabolites that were uniquely produced by one species or the other were identified. Specifically, the virulence factor precursor anthranilic acid as well as the quinoline 2,4-Quinolinediol (DHQ) were robustly produced across all tested strains of <em>P. aeruginosa</em>. Through the direct comparison of the extracellular metabolism of <em>P. aeruginosa</em> and <em>S. aureus</em> in a physiologically relevant environment, this work provides insight towards the potential metabolic interactions in vivo and supports the development of species-specific diagnostic markers of infection.</p>
2021-05-26 | MTBLS2105 | MetaboLights
Project description:Background: Chronic lung infection of cystic fibrosis (CF) patients by Staphylococcus aureus is a well-established epidemiological fact. Indeed, S. aureus is the most commonly identified pathogen in the lungs of CF patients. Strikingly the molecular mechanisms underlying S. aureus persistency are not understood. Methods: To gain insights into S. aureus adaptation to CF lungs, we selected pairs of sequential S. aureus isolates from 3 patients with CF and from one patient with non-CF chronic lung disease. We used a combination of genomic, proteomic and metabolomic approaches with functional assays for in-depth characterization of S. aureus long-term persistence during chronic lung infection. Results: For the first time, we show that late S. aureus isolates from CF patients have an increased ability for intracellular survival in CFBE-F508del cells compared to ancestral early isolates. Importantly, the increased ability to persist intracellularly was confirmed for S. aureus isolates within the own patient F508del epithelial cells. An increased ability to form biofilm was also demonstrated. Furthermore, to explain observed phenotypic adaptations, we identified the underlying genetic modifications inducing altered protein expression profiles and notable metabolic changes. These modifications affect several metabolic pathways (e.g., pantothenate and fatty acids) and virulence regulators (encoded by agr and sae loci) that could constitute therapeutic targets. Conclusions: Our results strongly suggest that the intracellular environment might constitute an important niche of persistence and relapse necessitating adapted antibiotic treatments.
2021-03-29 | PXD011281 | Pride
Project description:Chronic Pseudomonas aeruginosa infections evades antibiotic therapy and are associated with mortality in cystic fibrosis (CF) patients. We find that in vitro resistance evolution of P.aeruginosa towards clinically relevant antibiotics leads to phenotypic convergence towards distinct states. These states are associated with collateral sensitivity towards several antibiotic classes and encoded by mutations in antibiotic resistance genes, including transcriptional regulator nfxB. Longitudinal analysis of isolates from CF patients reveals similar and defined phenotypic states, which are associated with extinction of specific sub-lineages in patients. In depth investigation of chronic P.aeruginosa populations in a CF patient during antibiotic therapy revealed dramatic genotypic and phenotypic convergence. Notably, fluoroquinolone-resistant subpopulations harboring nfxB mutations were eradicated by antibiotic therapy as predicted by our in vitro data. This study supports the hypothesis that antibiotic treatment of chronic infections can be optimized by targeting phenotypic states associated with specific mutations to improve treatment success in chronic infections.
2018-10-23 | PXD007972 | Pride
Project description:Genome Sequence of Staphylococcus aureus Cystic Fibrosis Isolates
| PRJNA480016 | ENA
Project description:Staphylococcus aureus in cystic fibrosis
| PRJNA721116 | ENA
Project description:Staphylococcus aureus is a notorious bacterial pathogen that causes a broad range of human diseases, and isolates that are resistant to several antibiotic classes including last resort antibiotics like vancomycin and daptomycin complicate the situation. We characterized S. aureus VC40, a strain that shows full resistance to vancomycin (MIC of 64 M-BM-5g/ml) and daptomycin (MIC of 4 M-BM-5g/ml) as well as a decreased susceptibility to further cell wall active agents. Genome sequencing revealed mutations in genes encoding the histidine kinases WalK and VraS that control cell envelope related processes and gene expression profiling indicated the induction of the respective regulons in strain VC40. Reconstitution of the mutations in walK or vraS into the susceptible S. aureus NCTC 8325 background resulted in a considerably increased resistance to vancomycin and daptomycin with MICs surpassing the clinical breakpoints for these antibiotics, thereby generating vancomycin-intermediate S. aureus (VISA) strains. As observed for S. aureus VC40, the walKwalk and vraS mutations also led to an increased expression of the respective regulons in the NCTC 8325 background. Phenotypic studies showed that S. aureus VC40 as well as the walKwalk and vraS mutants of strain NCTC 8325 were characterized by a significantly thickened cell wall, a decreased growth rate, a reduced autolytic activity and an increased resistance to lysostaphin-induced lysis. These results demonstrate that the WalK and VraS histidine kinases act as major switches which allow S. aureus to rapidly develop vancomycin resistance up to the VISA level via mutation of one single gene locus and concomitantly contribute to cross-resistance to other antibiotics including the last resort antibiotic daptomycin. Microarray was used to evaluate alteration in the transcriptome of mutS mutant and compared to the parental strain VC40
2014-08-18 | E-GEOD-46887 | biostudies-arrayexpress