Browse
Submit Data
Databases
API
Help

Dataset Information

6 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Inhibition of staphylococcal alpha-toxin. A kinetic evaluation of aromatic polysulphonic acids as inhibitors of haemolysis.

ABSTRACT: 1. The effect of a number of aromatic polysulphonic acids on the kinetics of haemolysis of rabbit erythrocyte suspensions by crude staphylococcal alpha-toxin was studied at pH8.6 and 6.8. 2. All of the inhibitory compounds caused an increase in the prelytic lag time (tau) of the sigmoid haemolysis curves, an increase in the time to reach 50% haemolysis (t((1/2))) and a decrease in the maximum rate of haemolysis (R(max.)). The most inhibitory compounds caused a 50% decrease in R(max.) at concentrations between 0.1 and 0.2mm. 3. The effect of pH varied considerably: compounds (I) and (II) were almost equally inhibitory at both pH values, compounds (IV) and (IX) were more inhibitory at pH6.8 than at pH8.6, and compounds (VII), (VIII), (X), (XI) and (XII) were more inhibitory at pH8.6. 4. Increased time of premixing alpha-toxin with compound (I) caused increased inhibition. 5. An attempt was made, where possible, to relate the inhibitory activity to the structure of the test compound.

SUBMITTER: Wright MR

PROVIDER: S-EPMC1198767 | biostudies-other | 1968 Jun

REPOSITORIES: biostudies-other

ACCESS DATA

Json Xml

Similar Datasets

Inhibition of staphylococcal alpha-toxin. The effect of aromatic polysulphonic acids on the lethal effect of alpha-toxin in mice.

Project description:1. Certain aromatic polysulphonic acids, previously tested for inhibition of the haemolytic activity of staphylococcal alpha-toxin, together with some additional related compounds, were tested as possible inhibitors of alpha-toxin in mice. 2. Compounds that inhibited the haemolytic activity of alpha-toxin at concentrations of 0.16mm or less [compounds (I), (II), (IV), (V), (VII) and (VIII)] were found to inhibit the lethal effect of alpha-toxin. 3. With the exception of compound (VIII), amounts of 1mg. were required to inhibit 4 LD(50) of toxin when the test compounds were premixed with alpha-toxin before injection; comparable inhibition with 0.3mg. of compound (VIII) was achieved without prolonged premixing. 4. Mixtures of alpha-toxin and compounds (I) and (II) containing an excess of test compound showed markedly diminished inhibitory activities. 5. The ;half-molecule' analogues of group 1 [compounds (III) and (XVIII)] were non-inhibitory. 6. Compounds (I)-(V), when administered separately from alpha-toxin by the same route (intraperitoneal), were active only when injected almost simultaneously with toxin, whereas compounds (VII) and (VIII) were strikingly inhibitory when injected 15min. before or after the toxin. 7. Compound (VIII) failed to inhibit the lethal effect of alpha-toxin when injected by a different route (intravenous).

| S-EPMC1198768 | biostudies-other

Human OTULIN haploinsufficiency impairs cell-intrinsic immunity to staphylococcal α-toxin

Project description:We performed single-cell RNA sequencing (scRNASeq) on cryopreserved peripheral blood mononuclear cells (PBMCs) of healthy controls and OTULIN haploinsufficient patients in order to clarify the perturbation, if any, of cellular phenotypes in various leukocyte subsets in vivo at basal state attributable to OTULIN haploinsufficiency.

2023-04-01 | GSE199445 | GEO

Interferon-? Protects from Staphylococcal Alpha Toxin-Induced Keratinocyte Death through Apolipoprotein L1.

Project description:Staphylococcus aureus is a bacterial pathogen that frequently infects the skin, causing lesions and cell destruction through its primary virulence factor, alpha toxin. Here we show that interferon gamma (IFN-?) protects human keratinocytes from cell death induced by staphylococcal alpha toxin. We find that IFN-? prevents alpha toxin binding and reduces expression of the alpha toxin receptor, a disintegrin and metalloproteinase 10 (ADAM10). We determine that the mechanism for IFN-?-mediated resistance to alpha toxin involves the induction of autophagy, a process of cellular adaptation to sublethal damage. We find that IFN-? potently stimulates activation of the primary autophagy effector, light chain 3 (LC3). This process is dependent on upregulation of apolipoprotein L1. Depletion of apolipoprotein L1 by small interfering RNA significantly increases alpha toxin-induced lethality and inhibits activation of light chain 3. We conclude that IFN-? plays a significant role in protecting human keratinocytes from the lethal effects of staphylococcal alpha toxin through apolipoprotein L1-induced autophagy.

| S-EPMC4808518 | biostudies-literature

Staphylococcal alpha-toxin is not sufficient to mediate escape from phagolysosomes in upper-airway epithelial cells.

Project description:Intracellular Staphylococcus aureus has been implicated in the establishment of chronic infections. It is therefore imperative to understand by what means S. aureus is able to survive within cells. Here we use two expression systems with a fluorescent readout to assay alpha-toxin expression and function within phagolysosomes of infected upper-airway epithelial cells: avirulent Staphylococcus carnosus TM300 and phenotypically alpha-toxin-negative S. aureus laboratory strains. Data from CFU recovery assays suggest that the presence of alpha-toxin is not beneficial for the intracellular survival of recombinant Staphylococcus strains. This finding was corroborated by immunofluorescence studies: whereas S. carnosus and S. aureus are able to deliver S. aureus alpha-toxin to lumina of host cell phagolysosomes, the membrane integrity of these organelles was not affected. Alpha-toxin-expressing strains were detected exclusively within lysosome-associated membrane protein 1 (LAMP1)-yellow fluorescent protein (YFP)-positive vesicles. Measurements of intraphagosomal pH illustrated that all infected phagolysosomes acidified regardless of alpha-toxin expression. In contrast, S. aureus expressing Listeria monocytogenes listeriolysin O leads to the breakdown of the phagolysosomal membrane, as indicated by staphylococci that are not associated with LAMP1-YFP-decorated vesicles and that do not reside within an acidic cellular environment. Thus, our results suggest that staphylococcal alpha-toxin is not sufficient to mediate phagolysosomal escape in upper-airway epithelial cells.

| S-EPMC2738027 | biostudies-literature

Direct Synthesis of ?-Thio Aromatic Acids from Aromatic Amino Acids.

Project description:Modified amino acids are useful synthetic components in both chemistry and biology. Here we describe a simple, scalable two-step procedure to generate ?-thio aromatic acids from aromatic amino acids with yields of up to 96%. Diazotization and ?-lactone mediated bromination efficiently form the ?-bromo acid with retention of configuration. Thiol substitution with mild reagents such as sodium hydrosulfide or sodium trithiocarbonate provides the inverted, free ?-thio acid. The mildly acidic soft nucleophile can then be utilized in many synthetic applications.

| S-EPMC6101259 | biostudies-literature

Haemolysis induced by tyrosine crystals: Modifiers and inhibitors.

Project description:Tyrosine as a solid, but not in solution, caused human erythrocyte haemolysis. Haemolysis was increased with higher tyrosine concentrations and extended incubation times; it was greater at 37degrees than 4degreesC, and decreased by higher erythrocyte concentrations. Titration of phenolic groups on the surface of di-iodotyrosine crystals altered the extent of di-iodotyrosine-induced haemolysis. Haemolysis induced by tyrosine was inhibited by polyethylene glycol (mol.wt. 6000 or 20000) in a competitive fashion; polyoxyethylene/polyoxypropylene non-ionic detergents, polyvinylpyrrolidone (mol.wt. 40000 or 360000), 0.25--1.0M-NaC1, 0.25--1.0 M-KC1 and 0.25 M-NaSCN also inhibited haemolysis. H+-ion donation from the phenolic groups of tyrosine is suggested as part of the mechanism of haemolysis. Non-ionic detergents may inhibit tyrosine-crystal-induced haemolysis by binding the phenolic groups at the surface of the crystal.

| S-EPMC1163931 | biostudies-other

Hydrophobic amino acids as a new class of kinetic inhibitors for gas hydrate formation.

Project description:As the foundation of energy industry moves towards gas, flow assurance technology preventing pipelines from hydrate blockages becomes increasingly significant. However, the principle of hydrate inhibition is still poorly understood. Here, we examined natural hydrophobic amino acids as novel kinetic hydrate inhibitors (KHIs), and investigated hydrate inhibition phenomena by using them as a model system. Amino acids with lower hydrophobicity were found to be better KHIs to delay nucleation and retard growth, working by disrupting the water hydrogen bond network, while those with higher hydrophobicity strengthened the local water structure. It was found that perturbation of the water structure around KHIs plays a critical role in hydrate inhibition. This suggestion of a new class of KHIs will aid development of KHIs with enhanced biodegradability, and the present findings will accelerate the improved control of hydrate formation for natural gas exploitation and the utilization of hydrates as next-generation gas capture media.

| S-EPMC3741619 | biostudies-literature

Defining the strain-dependent impact of the Staphylococcal accessory regulator (sarA) on the alpha-toxin phenotype of Staphylococcus aureus.

Project description:We demonstrate that mutation of the staphylococcal accessory regulator (sarA) limits the accumulation of alpha-toxin and phenol-soluble modulins (PSMs) in Staphylococcus aureus isolates of the USA300 clonal lineage. Degradation assays and experiments done with protease inhibitors suggested that this was due to the increased production of extracellular proteases rather than differences associated with the impact of sarA on transcription of the target gene (hla) or the accessory gene regulator (agr). This was confirmed by demonstrating that concomitant mutation of the gene encoding aureolysin (aur) reversed the alpha-toxin and PSM-deficient phenotypes of a USA300 sarA mutant. Mutation of sarA had little impact on the alpha-toxin or PSM phenotypes of the commonly studied strain Newman, which is known to have a mutation in saeS that results in constitutive activation of the saeRS regulatory system, and we also demonstrate that repair of this defect resulted in the increased production of extracellular proteases and reversed both the alpha-toxin and PSM-positive phenotypes of a Newman sarA mutant.

| S-EPMC3133183 | biostudies-literature

α-Triazolylboronic Acids: A Promising Scaffold for Effective Inhibitors of KPCs.

Project description:Boronic acids are known reversible covalent inhibitors of serine β-lactamases. The selectivity and high potency of specific boronates bearing an amide side chain that mimics the β-lactam's amide side chain have been advanced in several studies. Herein, we describe a new class of boronic acids in which the amide group is replaced by a bioisostere triazole. The boronic acids were obtained in a two-step synthesis that relies on the solid and versatile copper-catalyzed azide-alkyne cycloaddition (CuAAC) followed by boronate deprotection. All of the compounds show very good inhibition of the Klebsiella pneumoniae carbapenemase KPC-2, with Ki values ranging from 1 nM to 1 μM, and most of them are able to restore cefepime activity against K. pneumoniae harboring blaKPC-2 . In particular, compound 1 e, bearing a sulfonamide substituted by a thiophene ring, proved to be an excellent KPC-2 inhibitor (Ki =30 nM); it restored cefepime susceptibility in KPC-Kpn cells (MIC=0.5 μg/mL) with values similar to that of vaborbactam (Ki =20 nM, MIC in KPC-Kpn 0.5 μg/mL). Our findings suggest that α-triazolylboronates might represent an effective scaffold for the treatment of KPC-mediated infections.

| S-EPMC8256004 | biostudies-literature

Synthesis and kinetic evaluation of 4-deoxymaltopentaose and 4-deoxymaltohexaose as inhibitors of muscle and potato alpha-glucan phosphorylases.

Project description:alpha-Glucan phosphorylases degrade linear or branched oligosaccharides via a glycosyl transfer reaction, occurring with retention of configuration, to generate alpha-glucose-1-phosphate (G1P). We report here the chemoenzymic synthesis of two incompetent oligosaccharide substrate analogues, 4-deoxymaltohexaose (4DG6) and 4-deoxymaltopentaose (4DG5), for use in probing this mechanism. A kinetic analysis of the interactions of 4DG5 and 4DG6 with both muscle and potato phosphorylases was completed to provide insight into the nature of the binding mode of oligosaccharide to phosphorylase. The 4-deoxy-oligosaccharides bind competitively with maltopentaose and non-competitively with respect to orthophosphate or G1P in each case, indicating binding in the oligosaccharide binding site. Further, 4DG5 and 4DG6 were found to bind to potato and muscle phosphorylases some 10-40-fold tighter than does maltopentaose. Similar increases in affinity as a consequence of 4-deoxygenation were observed previously for the binding of polymeric glycogen analogues to rabbit muscle phosphorylase [Withers (1990) Carbohydr. Res. 196, 61-73].

| S-EPMC1220049 | biostudies-other

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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