Browse
Submit Data
Databases
API
Help

Dataset Information

3 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Inhibition of MurA Enzyme from Escherichia coli and Staphylococcus aureus by Diterpenes from Lepechinia meyenii and Their Synthetic Analogs.

ABSTRACT: Enzymes MurA and MurF, involved in bacterial cell wall synthesis, have been validated as targets for the discovery of novel antibiotics. A panel of plant-origin antibacterial diterpenes and synthetic analogs derived therefrom were investigated for their inhibitory properties on these enzymes from Escherichia coli and Staphylococcus aureus. Six compounds were proven to be effective for inhibiting MurA from both bacteria, with IC₅₀ values ranging from 1.1 to 25.1 µM. To further mechanistically investigate the nature of binding and to explain the activity, these compounds were docked into the active site of MurA from E. coli. The aromatic ring of the active compounds showed a T-shaped π-π interaction with the phenyl ring of Phe328, and at least one hydrogen bond was formed between the hydroxy groups and Arg120 and/or Arg91. The results disclosed here establish new chemical scaffolds for the development of novel entities targeting MurA as potential antibiotics to combat the threat of pathogenic bacteria, particularly resistant strains.

SUBMITTER: Funes Chaban M

PROVIDER: S-EPMC8698320 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Inhibition of MurA Enzyme from Escherichia coli by Flavonoids and Their Synthetic Analogues.

Project description:MurA catalyzes the first step of peptidoglycan (PG) biosynthesis and is a validated target for the development of new antimicrobial agents. In this study, a library of 49 plant flavonoids and their synthetic derivatives were evaluated for their inhibitory properties against MurA fromEscherichia coli. The compounds were tested with and without preincubation and with the addition of DTT to understand the mechanism of inhibition. Thirteen compounds were identified as reversible, time-dependent inhibitors, with inhibition levels ranging from 480 nM to 57 μM, and ampelopsin as the most potent compound. To investigate the major pharmacophore elements responsible for the activity, 2D-QSAR and docking analyzes were performed. The results showed that the catechol moiety and an additional aromatic system were the most important features contributing to the activity of the compounds. However, most of the compounds did not show antibacterial activity againstE. coli andStaphylococcus aureusstrains, suggesting that their inhibitory activity against MurA may not be strong enough to induce antibacterial effects. Nevertheless, our results suggest that flavonoids are a promising starting point to develop new inhibitors of MurA and show great potential for further steps in drug development.

| S-EPMC10500568 | biostudies-literature

Separation and Identification of Antioxidants and Aldose Reductase Inhibitors in Lepechinia meyenii (Walp.) Epling.

Project description:We previously reported that Lepechinia meyenii (Walp.) Epling has antioxidant and aldose reductase (AR) inhibitory activities. In this study, L. meyenii was extracted in a 50% MeOH and CH2Cl2/MeOH system. The active extracts of MeOH and 50% MeOH were subjected to fractionation, followed by separation using high-speed counter-current chromatography (HSCCC) and preparative HPLC. Separation and identification revealed the presence of caffeic acid, hesperidin, rosmarinic acid, diosmin, methyl rosmarinate, diosmetin, and butyl rosmarinate. Of these, rosmarinic acid, methyl rosmarinate, and butyl rosmarinate possessed remarkable antioxidant and AR inhibitory activities. The other compounds were less active. In particular, rosmarinic acid is the key contributor to the antioxidant and AR inhibitory activities of L. meyenii; it is rich in the MeOH extract (333.84 mg/g) and 50% MeOH extract (135.41 mg/g) of L. meyenii and is especially abundant in the EtOAc and n-BuOH fractions (373.71-804.07 mg/g) of the MeOH and 50% MeOH extracts. The results clarified the basis of antioxidant and AR inhibitory activity of L. meyenii, adding scientific evidence supporting its traditional use as an anti-diabetic herbal medicine. The HSCCC separation method established in this study can be used for the preparative separation of rosmarinic acid from natural products.

| S-EPMC8707451 | biostudies-literature

Antibiofilm Activities of Cinnamaldehyde Analogs against Uropathogenic Escherichia coli and Staphylococcus aureus.

Project description:Bacterial biofilm formation is a major cause of drug resistance and bacterial persistence; thus, controlling pathogenic biofilms is an important component of strategies targeting infectious bacterial diseases. Cinnamaldehyde (CNMA) has broad-spectrum antimicrobial and antibiofilm activities. In this study, we investigated the antibiofilm effects of ten CNMA derivatives and trans-CNMA against Gram-negative uropathogenic Escherichia coli (UPEC) and Gram-positive Staphylococcus aureus. Among the CNMA analogs tested, 4-nitrocinnamaldehyde (4-nitroCNMA) showed antibacterial and antibiofilm activities against UPEC and S. aureus with minimum inhibitory concentrations (MICs) for cell growth of 100 µg/mL, which were much more active than those of trans-CNMA. 4-NitroCNMA inhibited UPEC swimming motility, and both trans-CNMA and 4-nitroCNMA reduced extracellular polymeric substance production by UPEC. Furthermore, 4-nitroCNMA inhibited the formation of mixed UPEC/S. aureus biofilms. Collectively, our observations indicate that trans-CNMA and 4-nitroCNMA potently inhibit biofilm formation by UPEC and S. aureus. We suggest efforts be made to determine the therapeutic scope of CNMA analogs, as our results suggest CNMA derivatives have potential therapeutic use for biofilm-associated diseases.

| S-EPMC9267110 | biostudies-literature

Synthesis of Degraded Limonoid Analogs as New Antibacterial Scaffolds against Staphylococcus aureus.

Project description:Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA) have become serious infections in humans and ruminants. S. aureus strains are showing rapid changes to develop resistance in traditional antibiotic-containing systems. In the continuous fierce fight against the emergent multi-drug resistant bacterial strains, straightforward and scalable synthetic procedures to produce new active molecules are in demand. Analysis of molecular properties points to degraded limonoids as promising candidates. In this article, we report a simple synthetic approach to obtain degraded limonoid analogs as scaffolds for new antibacterial molecules. The minimum inhibitory concentrations against S. aureus were evaluated for the stereoisomer mixtures by the broth microdilution method. Analysis of results showed that the acetylated derivatives were the most active of them all.

| S-EPMC7459938 | biostudies-literature

Novel synthetic antimicrobial peptides effective against methicillin-resistant Staphylococcus aureus.

Project description:Previously, we identified a core undecapeptide of sapecin B having antimicrobial activity. Based on the structure of this peptide, we systematically synthesized peptides consisting of terminal basic motifs and internal oligo-leucine sequences and examined their antimicrobial activities. Of these peptides, RLKLLLLLRLK-NH2 and KLKLLLLLKLK-NH2 were found to have potent microbicidal activity against Staphylococcus aureus, Escherichia coli, methicillin-resistant S. aureus and Candida albicans in liquid medium. We also synthesized the D-enantiomer of KLKLLLLLKLK-NH2. This enantiomer was resistant to tryptic digestion and persisted longer in the culture medium, showing greater antimicrobial activity than the original peptide.

| S-EPMC1137260 | biostudies-other

Antibiotic Activity of Escherichia coli against Multiresistant Staphylococcus aureus.

Project description: Not available

| S-EPMC5075125 | biostudies-literature

Analogs of Eap protein are conserved and prevalent in clinical Staphylococcus aureus isolates.

Project description:Map and Eap are secreted Staphylococcus aureus proteins that interact with various extracellular matrix molecules. PCR analysis using map primers yielded positive reactions in 97.9% of S. aureus isolates but not in Staphylococcus epidermidis isolates. Cloning and sequencing of the conferring genes revealed a high degree of overall homology combined with size variability of the gene product due to various repeat numbers and early translation termination in a poly(A) region. Thus, Map and Eap may provide a potential novel tool for S. aureus identification and typing.

| S-EPMC96261 | biostudies-literature

Staphylococcus aureus Cas9 is a multiple-turnover enzyme.

Project description:Cas9 nuclease is the key effector of type II CRISPR adaptive immune systems found in bacteria. The nuclease can be programmed by a single guide RNA (sgRNA) to cleave DNA in a sequence-specific manner. This property has led to its widespread adoption as a genome editing tool in research laboratories and holds great promise for biotechnological and therapeutic applications. The general mechanistic features of catalysis by Cas9 homologs are comparable; however, a high degree of diversity exists among the protein sequences, which may result in subtle mechanistic differences. S. aureus (SauCas9) and especially S. pyogenes (SpyCas9) are among the best-characterized Cas9 proteins and share ∼17% sequence identity. A notable feature of SpyCas9 is an extremely slow rate of reaction turnover, which is thought to limit the amount of substrate DNA cleavage. Using in vitro biochemistry and enzyme kinetics, we directly compare SpyCas9 and SauCas9 activities. Here, we report that in contrast to SpyCas9, SauCas9 is a multiple-turnover enzyme, which to our knowledge is the first report of such activity in a Cas9 homolog. We also show that DNA cleaved with SauCas9 does not undergo any detectable single-stranded degradation after the initial double-stranded break observed previously with SpyCas9, thus providing new insights and considerations for future design of CRISPR/Cas9-based applications.

| S-EPMC6298560 | biostudies-literature

A type IV modification-dependent restriction enzyme SauUSI from Staphylococcus aureus subsp. aureus USA300.

Project description:A gene encoding a putative DNA helicase from Staphylococcus aureus USA300 was cloned and expressed in Escherichia coli. The protein was purified to over 90% purity by chromatography. The purified enzyme, SauUSI, predominantly cleaves modified DNA containing 5mC and 5-hydroxymethylcytosine. Cleavage of 5mC-modified plasmids indicated that the sites S5mCNGS (S = C or G) are preferentially digested. The endonuclease activity requires the presence of adenosine triphosphate (ATP) or dATP whereas the non-hydrolyzable γ-S-ATP does not support activity. SauUSI activity was inhibited by ethylenediaminetetraacetic acid. It is most active in Mg(++) buffers. No companion methylase gene was found near the SauUSI restriction gene. The absence of a cognate methylase and cleavage of modified DNA indicate that SauUSI belongs to type IV restriction endonucleases, a group that includes EcoK McrBC and Mrr. SauUSI belongs to a family of highly similar homologs found in other sequenced S. aureus, S. epidermidis and S. carnosus genomes. More distant SauUSI orthologs can be found in over 150 sequenced bacterial/archaea genomes. Finally, we demonstrated the biological function of the type IV REase in restricting 5mC-modified plasmid DNA by transformation into clinical S. aureus strain SA564, and in restricting phage λ infection when the endonuclease is expressed in E. coli.

| S-EPMC3141236 | biostudies-literature

Antimicrobial Peptide Induced-Stress Renders Staphylococcus aureus Susceptible to Toxic Nucleoside Analogs.

Project description:Cationic antimicrobial peptides (AMPs) are active immune effectors of multicellular organisms and are also considered as new antimicrobial drug candidates. One of the problems encountered when developing AMPs as drugs is the difficulty of reaching sufficient killing concentrations under physiological conditions. Here, using pexiganan, a cationic peptide derived from a host defense peptide of the African clawed frog and the first AMP developed into an antibacterial drug, we studied whether sub-lethal effects of AMPs can be harnessed to devise treatment combinations. We studied the pexiganan stress response of Staphylococcus aureus at sub-lethal concentrations using quantitative proteomics. Several proteins involved in nucleotide metabolism were elevated, suggesting a metabolic demand. We then show that Staphylococcus aureus is highly susceptible to antimetabolite nucleoside analogs when exposed to pexiganan, even at sub-inhibitory concentrations. These findings could be used to enhance pexiganan potency while decreasing the risk of resistance emergence, and our findings can likely be extended to other antimicrobial peptides.

| S-EPMC7550632 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data