Ontology highlight
ABSTRACT:
PROVIDER: PRJNA851374 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Multi-drug Resistant Gram-negative Bacteria - CCHE57357
| PRJNA603448 | ENA
Project description:GCID Multi-drug resistant Gram-negative clinical isolates from Thailand
| PRJNA389557 | ENA
Project description:Guanidine DNA quadruplex (G4-DNA) structures convey a distinctive layer of epigenetic information that is critical for the regulation of key biological activities and processes as genome transcription regulation, replication and repair. Despite several works that have been published recently, the information regarding their role and possible use as therapeutic drug targets in bacteria is still scarce. Here, we tested the biological activity of a small G4-DNA ligand library based on the naphthalene diimide (NDI) pharmacophore, against both Gram-positive and Gram-negative bacteria. For the best compound identified, NDI-10, the action mechanism was further characterized. Gram-negative bacteria were more resistant altogether due to the presence of the outer membrane, although the activity of the G4-Ligand was generally bactericidal, while it was bacteriostatic for Gram-positive bacteria. This asymmetric activity could be related to the different prevalence of putative G4-DNA structures in each group, the influence that they can exert on the gene expression (which was found more severe for the Gram-negative bacteria) and the role of the G4 structures in these bacteria, that seems to be more related to promote transcription in Gram-positive bacteria and repress transcription in Gram-negative.
2022-12-10 | GSE178890 | GEO
Project description:With the global increase in the use of carbapenems, several gram-negative bacteria have acquired carbapenem resistance, thereby limiting treatment options. Klebsiella pneumoniae is one of such notorious pathogen that is being widely studied to find novel resistance mechanisms and drug targets. These antibiotic-resistant clinical isolates generally harbor many genetic alterations, and identification of causal mutations will provide insights into the molecular mechanisms of antibiotic resistance. We propose a method to prioritize mutated genes responsible for antibiotic resistance, in which mutated genes that also show significant expression changes among their functionally coupled genes become more likely candidates. For network-based analyses, we developed a genome-scale co-functional network of K. pneumoniae genes, KlebNet (www.inetbio.org/klebnet). Using KlebNet, we could reconstruct functional modules for antibiotic-resistance, and virulence, and retrieved functional association between them. With complementation assays with top candidate genes, we could validate a gene for negative regulation of meropenem resistance and four genes for positive regulation of virulence in Galleria mellonella larvae. Therefore, our study demonstrated the feasibility of network-based identification of genes required for antimicrobial resistance and virulence of human pathogenic bacteria with genomic and transcriptomic profiles from antibiotic-resistant clinical isolates.
2018-06-10 | GSE115539 | GEO
Project description:A gram-negative bacteria which parasitizes other gram-negative bacteria.
| PRJNA12622 | ENA
Project description:There is an urgent need for novel antibiotics against carbapenem and 3rd generation cephalosporin-resistant Gram-negative pathogens, for which the last-resort antibiotics have lost most of their efficacy. We describe here a novel class of synthetic antibiotics that was inspired from natural product-derived scaffolds. The antibiotics have an unprecedented mechanism of action, which targets the main component (BamA) of the Bam folding machinery required for folding and insertion of ß-barrel proteins into the outer membrane of Gram-negative bacteria. This OMPTA (outer membrane protein-targeting antibiotic) class shows potent activity against multidrug-resistant Gram-negative ESKAPE pathogens and overcomes colistin-resistance both in vitro and in vivo. A clinical candidate has the potential to address life threatening Gram-negative infections with high unmet medical need.
2020-02-04 | MSV000084899 | MassIVE
Project description:There is an urgent need for novel antibiotics against carbapenem and 3rd generation cephalosporin-resistant Gram-negative pathogens, for which the last-resort antibiotics have lost most of their efficacy. We describe here a novel class of synthetic antibiotics that was inspired from natural product-derived scaffolds. The antibiotics have an unprecedented mechanism of action, which targets the main component (BamA) of the Bam folding machinery required for folding and insertion of ß-barrel proteins into the outer membrane of Gram-negative bacteria. This OMPTA (outer membrane protein-targeting antibiotic) class shows potent activity against multidrug-resistant Gram-negative ESKAPE pathogens and overcomes colistin-resistance both in vitro and in vivo. A clinical candidate has the potential to address life threatening Gram-negative infections with high unmet medical need.
2019-10-22 | PXD010174 | Pride