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PubMed2025

PqsE adapts the activity of the Pseudomonas aeruginosa quorum-sensing transcription factor RhlR to both autoinducer concentration and promoter sequence identity.

Pseudomonas aeruginosa is an opportunistic human pathogen that poses a significant health threat. Many pathogenic behaviors of P. aeruginosa are under control of the bacterial cell-cell communication system known as quorum sensing (QS). One of the QS master regulators, RhlR, is a receptor/transcription factor that not only relies on binding of its canonical ligand, N-butyrylhomoserine lactone (C4-HSL), but additionally requires a protein-protein interaction with the enzyme, PqsE. We constructed heterologous reporter strains in Escherichia coli that allow measurements of the reliance of RhlR on C4-HSL and/or PqsE binding for the ability to activate transcription of three RhlR-regulated genes: rhlA (PqsE independent), phzM (PqsE dependent), and azeB (PqsE inhibited). Analogous assays measuring activation of the three genes in P. aeruginosa were performed, and the patterns observed correlated tightly with the heterologous reporter assays. These results confirm that the binding of PqsE to RhlR is able to fine-tune RhlR transcription factor activity in a promoter-specific manner and prove that this ability is independent of other factors present in P. aeruginosa.IMPORTANCEPseudomonas aeruginosa is an opportunistic human pathogen that can cause fatal infections. There exists an urgent need for new, effective antimicrobial agents to combat P. aeruginosa. The PqsE-RhlR protein-protein interaction is essential for P. aeruginosa to be able to make toxins, form biofilms, and infect host organisms. In this study, we use both non-native models in Escherichia coli and measurements of gene expression/toxin production in P. aeruginosa to show that the PqsE-RhlR interaction enables fine-tuned gene expression and a heightened ability of P. aeruginosa to adapt to external conditions. These findings will be highly valuable as continued efforts are made to design inhibitors of the PqsE-RhlR interaction and test them as potential antimicrobial agents against P. aeruginosa infections.

Pseudomonas aeruginosa↗
PubMed1978

Synthesis of and allergic contact dermatitis to bicyclo-[2,2,1]-heptyl-alpha-methylene-gamma-butyrolactones derived from norbornene and camphene.

Three new lactones, 2-oxo-3-methylene-4,7-methanobenzofuran and two alpha-methylene spirolactones, 3',3'-dimethylspiro(2-oxo-3-methylenefuran-5,2'-norbornane), were synthesized and their skin activity was tested on one human volunteer and on guinea pigs. The man, sensitized to Frullania, was found sensitive to the above lactones and also reacted to frullanolide and alantolactone. The guinea pigs, experimentally sensitized to alantolactone, cross-reacted to 2-oxo-3-methylene-4,7-methanobenzofuran and the two alpha-methylene spirolactones, and also to isolantolactone and frullanolide.

4-Butyrolactone↗
PubMed1979

Effect of heparin on the metabolism of putrescine in vivo.

Rats and guinea pigs which are given heparin metabolize intraperitoneally injected [14C]-putrescine to 14CO2 at reduced rates. The results have been considered in relation to the heparin-induced liberation of diamine oxidase from tissues into the blood stream.

4-Butyrolactone↗
PubMed1979

A comparison of the effects of gamma-hydroxybutyrate and gamma-butyrolactone on cerebral carbohydrate metabolism.

The metabolic effects of 60-min exposure to 250-2000 mg gamma-hydroxybutyrate (GHB) per kilogram or 150-1200 mg gamma-butyrolactone (GBL) per kilogram were studied in rats by measurement of the cerebral hemisphere contents of energy phosphates and glycolytic-Krebs' cycle metabolites. A general pattern of increased glycogen and glucose with decreased pyruvate, lactate, alpha-ketoglutarate, and malate was observed. This pattern in association with unchanged adenylates and decreased energy phosphate utilization was consistent with a metabolic adaptation to a state of cerebral depression. The major qualitative difference between the two drugs was that higher doses of GBL were associated with additional decreases of citrate and glutamate. Since these doses of GBL were also associated with acute increases of arterial CO2 tension, it is proposed that these differences were secondary to hypercapnia and not due to a distinctive primary action of GBL. Derivation of the cytoplasmic NAD(P)H:NAD(P)+ ratios indicated that GHB and GBL were not associated with consistent alterations of the cytoplasmic redox state.

4-Butyrolactone↗
PubMedDate not supplied

Influence of various agents on the development of brain edema in the rat following microembolism. Protective effect of gamma-butyrolactone.

Brain edema was induced in rats by injecting 50 mu microspheres, labelled with 85Sr, into the internal carotid artery. The use of radioactive microspheres as embolic agents enabled the number of microspheres to be determined in each cerebral hemisphere. Edema was assessed 12 or 24 h after embolization by measuring brain water content and, in some experiments, sodium and potassium. Pretreatments with dexamethasone, parachlorophenylalanine (an inhibitor of 5-hydroxytryptamine synthesis), mepyramine and metiamide (H1 and H2 histamine receptor antagonists) or aminophylline did not influence significantly the development of brain edema evaluated 24 h after embolization. Aminophylline treatment (100 mg/kg) markedly increased mortality following embolization. Gamma-butyrolactone (300 mg/kg, every 2 h) inhibited significantly the development of brain edema evaluated 12 hours after embolization. Increases in water and sodium in the embolized cerebral hemisphere were reduced by about 50%. This protective effect may be related to the known depressant action on brain metabolism.

4-Butyrolactone↗
PubMed1979

Influence of A-factor on the ultrastructure of the A-factor deficient mutant of Streptomyces griseus.

The fine structure of the A-factor deficient mutant strain of Streptomyces griseus grown in the absence or in the presence of this factor was studied by transmission electron microscopy. The submerged 96 h culture grown in the presence of the A-factor was characterized by the formation of a large amount of spores accompanied by mycelium disintegration. A number of essential ultrastructural changes were observed in the mycelium in the course of development and streptomycin biosynthesis after the A-factor addition. Thus, the cell wall was transformed in another manner at various developmental stages. For a long time the associated ribosomes were preserved. The number of intracytoplasmic membrane structures increased. New, unusual organelles appeared which consisted of parallel cylindrical structures. The possible nature of these organelles is discussed.

4-Butyrolactone↗
PubMed1979

The effect of chronic ethanol administration on central neurotransmitter mechanisms.

Rats were maintained on ad lib food and a forced-intake regimen of ehtanol for up to 270 days. The ethanol treatment induced alterations in the metabolism of central catecholamines seen as increased endogenous concentrations of dopamine concomitantly with decreased concentrations of noradrenaline in the limbic forebrain. The synthesis of catecholamines, measured as the accumulation of dopa following inhibition of aromatic amino acid decarboxylase, was unchanged during chronic ethanol treatment. Local application of dopamine into the nucleus accumbens caused a greater increase in locomotor activity in chronic ethanol rats than in controls thus indicating that chronic ethanol treatment increased the sensitivity at or beyond central dopamine receptors. This phenomenon of functional dopamine receptor supersensitivity was first observed after 5 months of ethanol treatment and lasted for about 4 weeks after cessation of the ethanol treatment. The sensitivity of noradrenergic and cholinergic receptor mechanisms appeared to be unchanged after chronic exposure to ethanol. The effect of the GABAergic drug, gamma-butyrolactone (GBL) on the accumulation of dopa after inhibition of aromatic amino acid decarboxylase was studied in chronic ethanol rats. The enhancement of the dopa formation in dopaminergic neurons induced by GBL was markedly attenuated after chronic ethanol treatment. The gross behavioural depression by GBL was also weakened. This may indicate that chronic ethanol treatment causes subsensitivity of GABA receptors.

4-Butyrolactone↗
PubMed1977

Antimitotic and antitubulin activity of the tumor inhibitor steganacin.

Steganacin, a newly isolated tumor inhibitor, completely inhibits cleavage in sea urchin eggs at 3 X 10(-7) M by preventing the formation of the mitotic apparatus. Steganacin inhibits the polymerization of tubulin in vitro and also causes a slow depolymerization of preformed microtubules. Optical ultracentrifuge studies of steganacin-treated tubulin show a small reduction in 20 S and 30 S peaks at 0 degree. In electron microscope studies the ring structure of tubulin is seen at 0 degree but disappears if the temperature of tubulin incubated with steganacin is raised to 37 degrees. Steganacin inhibits the binding of colchicine to tubulin and thus resembles podophyllotoxin, which also competitively inhibits colchicine binding. Steganacin had a trimethoxybenzene ring and probably interacts with that portion of the colchicine-binding site that recognizes the trimethoxybenzene ring of colchicine.

4-Butyrolactone↗
PubMedDate not supplied

The central action of 1-p-dimethylaminophenyl-5-allyl-5-(beta-hydroxypropyl) barbituric acid and the corresponding lactone.

1-p-dimethylaminophenyl-5-allyl-5-(beta-hydroxypropyl)barbituric acid (NP) and the probably product of its isomerization alpha-(p-dimethylaminophenyl)allophanyl-alpha-allyl-gamma-methylbutyrolactone (MW) was studied. Behavioral experiments carried out on mice and rats showed that both the acid (NP) and the lactone (MW) suppress the reactivity of the central nervous system, and, to some degree, act like tranquilizing agents.

1-Propanol↗