Ontology highlight
ABSTRACT:
PROVIDER: PRJEB35546 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Various bis-benzimidazole derivatives have been reported to possess activity against Gram-positive pathogens. No mechanism of action has been elucidated to fully account for the antibacterial activity of this class of compounds. A group of symmetric bis-benzimidazoles (BBZ) designed as anticancer agents have previously been shown to possess moderate antiproliferative activity. We sought to assess the antibacterial activity and mechanism of action of BBZ compounds against Staphylococcus aureus. Antibacterial activities were assessed by determination of minimal inhibitory concentrations (MICs), time-kill curves, and scanning electron microscopy. Transcriptional responses to BBZ treatment were determined using whole genome microarrays. Activities against bacterial type II topoisomerases were investigated using in vitro supercoiling, decatenation, DNA binding, and DNA cleavage inhibition assays. MICs for EMRSA-16 were between 0.03 and 0.5 μg/mL. The compounds showed concentration-dependent bactericidal activity and induced cell swelling and lysis. Transcriptional responses to BBZ were consistent with topoisomerase inhibition and DNA damage. A subset of BBZ compounds inhibited S. aureus DNA gyrase supercoiling activity with IC50 values in the range of 5−10 μM. This inhibition was subsequently shown to operate through both inhibition of binding of DNA gyrase to DNA and accumulation of single-stranded DNA breaks. We conclude that BBZ compounds are potent antistaphylococcal agents and operate at least in part through DNA gyrase inhibition, leading to the accumulation of single-stranded DNA breaks, and by preventing the binding of gyrase to DNA. [Data is also available from http://bugs.sgul.ac.uk/E-BUGS-106]
2012-10-14 | E-BUGS-106 | biostudies-arrayexpress
Project description:CD44 is a transmembrane adhesion molecule and the major receptor for hyaluronan. The function of CD44 has been implicated in numerous biological processes. Our study finds that zebrafish CD44a variants function as positive regulators in antibacterial response. In order to reveal the possible antibacterial mechanism of CD44a, the wild-type and CD44a-/--14del zebrafish larvaes infected with E. piscicida collected at 24 and 48 hpi were used for transcriptome sequencing. Our data demonstrate that zebrafish CD44a functions as a regulator of p53 signaling, apoptosis and autophagy in the antibacterial immune response.
2021-07-26 | GSE180770 | GEO
Project description:Bacteria commonly adapt to stresses by altering gene expression. To understand the response of M. tuberculosis (MTB) to various antibacterial agents, we performed transcriptomics on MTB bacilli exposed to several test compounds as well as known drugs (capreomycin, cycloserine, ethionamide, isoniazid, kanamycin, moxifloxacin, PA-824, rifampicin, streptomycin).
2015-11-11 | GSE71200 | GEO
Project description:Objectives Pyrrolobenzodiazepine (PBD) dimers, tethered through inert propyldioxy or pentyldioxy linkers, possess potent bactericidal activity against a range of Gram-positive bacteria by virtue of their capacity to cross-link duplex DNA in sequence-selective fashion. Here we attempt to improve the antibacterial activity and cytotoxicity profile of PBD-containing conjugates by extension of dimer linkers and replacement of one PBD unit with phenyl-substituted or benzo-fused heterocycles that facilitate non-covalent interactions with duplex DNA. Methods DNase I footprinting was used to identify high-affinity DNA binding sites. A staphylococcal gene microarray was used to assess epidemic methicillin-resistant Staphylococcus aureus 16 phenotypes induced by PBD conjugates. Molecular dynamics simulations were employed to investigate the accommodation of compounds within the DNA helix. Results Increasing the length of the linker in PBD dimers led to a progressive reduction in antibacterial activity, but not in their cytotoxic capacity. Complex patterns of DNA binding were noted for extended PBD dimers. Modelling of DNA strand cross-linking by PBD dimers indicated distortion of the helix. A majority (26 of 43) of PBD-biaryl conjugates possessed potent antibacterial activity with little or no helical distortion and a more favourable cytotoxicity profile. Bactericidal activity of PBD-biaryl conjugates was determined by inability to excise covalently bound drug molecules from bacterial duplex DNA. Conclusions PBD-biaryl conjugates have a superior antibacterial profile compared with PBD dimers such as ELB-21. We have identified six PBD-biaryl conjugates as potential drug development candidates. [Data is also available from http://bugs.sgul.ac.uk/E-BUGS-118]
2012-04-17 | E-BUGS-118 | biostudies-arrayexpress
Project description:Lincomycin is a lincosamide antibiotic that forms cross-links within the peptidyl transferase loop region of the 23S rRNA of the 50S subunit of the bacterial ribosome, thereby inhibiting protein synthesis. We have previously reported that lincomycin at concentrations below the minimum inhibitory concentration potentiates the production of secondary metabolites in actinomycete strains. We aimed to elucidate the fundamental mechanisms underlying lincomycin induction of secondary metabolism in actinomycetes. Therefore, the dose-dependent response of lincomycin on gene expression of the model actinomycetes Streptomyces coelicolor A3(2) and possible relationships to secondary metabolism have been investigated.
2018-03-02 | E-MTAB-6434 | biostudies-arrayexpress