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Results for “toxin secretion system”

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PubMed1978

Cholera toxin effects on fluid secretion, adenylate cyclase, and cyclic AMP in porcine small intestine.

The effects of cholera toxin on mucosal cyclic nucleotide concentrations and on net fluid secretion in the porcine small intestine are reported. Cholera toxin causes net secretion of fluid into the small intestine of weanling pigs, and secretory rates are dependent on the dose of the toxin placed in intestinal loops. Intestinal secretion due to cholera toxin exposure was not consistently accompanied by elevated concentrations of mucosal cyclic AMP or cyclic GMP. Net fluid fluxes in individual loops did not correlate with mucosal cyclic AMP concentration in the same loop. Jejunal adenylate cyclase was activated to a lesser extent in pigs, compared with rabbits, after in vivo treatment with cholera toxin. In vitro activation in cell-free homogenates was similar for both species. Papaverine was similar to cholera toxin in causing fluid secretion without cyclic AMP accumulations, but 3-isobutyl-1-methyl xanthine significantly increased cyclic AMP concentration and induced fluid secretion in pigs. Weanling pigs appeared to differ from rabbits in having a secretory response to cholera toxin which was independent of elevations in total mucosal cyclic AMP concentration.

1-Methyl-3-isobutylxanthine↗

PubMed1978

The effect of cholera toxin and heat labile and heat stable Escherichia coli enterotoxin on cyclic AMP concentrations in small intestinal mucosa of pig and rabbit.

The effect of cholera toxin, heat labile and heat stable Escherichia coli enterotoxin on mucosal cyclic AMP concentrations was determined on the proximal jejunum of weanling pigs and young rabbits. Ligated loops were injected with solutions containing no enterotoxin for control and either cholera toxin, heat labile or heat stable E. coli enterotoxin. The loops were drained after either two, four or six hours incubation at which time accumulated fluid was recorded and mucosal samples removed for determination of cyclic AMP concentration. In the rabbit, cholera toxin and heat labile, but not heat stable E. coli enterotoxin stimulated intestinal secretion while in the pig all three enterotoxins induced net fluid accumulation. Cholera toxin and heat labile, but not heat stable E. coli enterotoxin elevated rabbit mucosal cyclic AMP concentrations. In the pig these enterotoxins had no significant effect on mucosal cyclic AMP concentrations. The results are inconsistent with the hypothesis that the adenyl cyclase system is an essential step for enterotoxin induced intestinal secretion. The activation of intestinal adenyl cyclase by bacterial enterotoxins may only be an associated and not a necessary event for the stimulation of intestinal secretion.

Animals↗

PubMed1978

Effect of heat stable and heat labile Escherichia coli enterotoxins and cholera toxin in combination with theophylline on unidirectional sodium and chloride flux in the small intestine of weanling swine.

The effect of heat stable and heat labile Escherichia coli enterotoxins or cholera toxin in combination with theophylline on net water, sodium and chloride and unidirectional sodium and chloride fluxes was examined in acute isolated loops of jejunum of weanling swine. The effect of heat stable enterotoxin in combination with theophylline was determined in loops located in the proximal jejunum, while combinations of theophylline and either heat labile enterotoxin or cholera toxin were studied in the distal jejunum. In each situation the addition of theophylline resulted in an additive rather than a synergistic increment of intestinal secretory activity. This study implies that the intestinal adenyl cyclase system and enterotoxin induced intestinal secretion may not be directly related in the swine small intestine.

Animals↗

PubMed1992

'In vitro' action of histamine and cimetidine on amylase secretion in the rat pancreas.

We report here the effect of histamine on amylase secretion in isolated lobules from the rat pancreas. Different concentrations of histamine increased amylase secretion, while the stimulatory effect was reduced by cimetidine although not by chlorpheniramine. These findings suggest that pancreatic lobules have H2 receptors. On the other hand, bethanechol induced a stimulatory effect on pancreatic lobules that was inhibited by cimetidine. Vibrio cholerae toxin stimulated amylase secretion, but this effect was not reduced by cimetidine. Cimetidine may thus block the stimulated amylase secretion interfering with the Ca2+ messenger system.

Amylases↗

PubMed1992

Secretion across the bacterial outer membrane.

Many bacteria secrete extracellular proteins such as hydrolytic enzymes or toxins. In Gram-negative bacteria, secreted proteins must cross the two membranes that constitute the cell envelope. Recent studies have identified several specific secretion systems that can be classified in three distinct pathways, and related systems have been discovered in a wide range of prokaryotic and eukaryotic cells.

Adenosine Triphosphate↗

PubMed1992

E. coli hemolysin interactions with prokaryotic and eukaryotic cell membranes.

The hemolysin toxin (HlyA) is secreted across both the cytoplasmic and outer membranes of pathogenic Escherichia coli and forms membrane pores in cells of the host immune system, causing cell dysfunction and death. The processes underlying the interaction of HlyA with the bacterial and mammalian cell membranes are remarkable. Secretion of HlyA occurs without a periplasmic intermediate and is directed by an uncleaved C-terminal targetting signal and the HlyB and HlyD translocator proteins, the former being a member of a transporter superfamily central to import and export of a wide range of substrates by prokaryotic and eukaryotic cells. The separate process by which HlyA is targetted to mammalian cell membranes is dependent upon fatty acylation of a non-toxic precursor, proHlyA. This is achieved by a novel mechanism directed by the activator protein HlyC, which binds to an internal proHlyA recognition sequence and provides specificity for the transfer of fatty acid from cellular acyl carrier protein.

Acylation↗

PubMed1992

A new model of human secretory diarrhoea using cholera toxin.

Secretory diarrhoea is a major cause of morbidity and mortality worldwide. However, there is no biologically relevant test system in man for assessing new anti-diarrhoeal therapies prior to clinical trial. We have used highly purified cholera toxin in combination with the triple lumen jejunal perfusion technique to establish a subclinical model of cholera in man. Cholera toxin was administered either by mouth with sodium bicarbonate or directly into a 30 cm 'open' or 'closed' (isolated between two inflated balloons) jejunal segment in healthy adult volunteers. Both oral dosing and direct delivery into an 'open' jejunal segment failed to produce consistent secretion of water and electrolytes. In contrast 15 micrograms or 25 micrograms of cholera toxin elicited secretion of water and sodium 3 h after instillation into the balloon occluded 'closed' jejunal segment (P less than 0.05 vs. controls). The rate of secretion was constant over the maximal period studied (4.5 h) and was similar to that reported in human cholera. None of the subjects experienced troublesome diarrhoea. We believe this model offers a relevant test system for assessing anti-diarrhoeal therapy in man.

Administration, Oral↗

PubMed1992

Interaction of ethanol with signal transduction mechanisms mediating growth hormone release by rat pituitary cells in vitro.

The effects of ethanol on signal transduction mechanisms of rat GH (rGH) release were investigated in primary culture of rat anterior pituitary cells. Ethanol (30, 100, and 300 mM) had no significant effect on basal rGH release or cell content after a 4-h incubation or on intracellular cAMP levels at 30 min. Ethanol did not alter rGRH (10(-11) M)-stimulated rGH release, but at concentrations of 100 and 300 mM it inhibited rGRH (10(-9) M)-stimulated rGH release by 12% (P less than 0.05) and 54% (P less than 0.01). In contrast, a dose-dependent stimulatory effect was observed on rGRH-induced cAMP accumulation. Ethanol enhanced the inhibitory effect of SRIH (10(-11) and 10(-9) M) on rGH release by up to 24% (P less than 0.01). Stimulation of rGH release by cAMP derivatives and forskolin was partially inhibited by ethanol, as was cAMP accumulation after forskolin treatment. Cholera toxin-stimulated rGH release was also inhibited by ethanol, whereas cAMP accumulation was increased. At the higher concentrations, ethanol enhanced rGH release after protein kinase-C activation by phorbol ester and after stimulation of calcium influx with Ca ionophore. No significant ethanol effect was noted on prostaglandin E2-stimulated rGH release, and ethanol did not alter rGH mRNA levels or proliferation of a pituitary somatomammotroph cell line. The results indicate that ethanol exerts multiple effects on systems mediating GH release from the pituitary in vitro. However, the inhibitory influence of ethanol on GH secretion is related primarily to the adenylate cyclase-cAMP pathway, which represents the major signal transducing system in the somatotroph.

Animals↗

PubMed1979

[Water and electrolytes intestinal secretion (author's transl)].

This paper reviews methods used for studying intestinal secretion in man and animals, fasting and post prandial intestinal secretion, as well as that induced by bacterial enterotoxins, hormonal stimuli, some endocrine tumours and various intraluminary agents; finally the possible mechanisms and sites of intestinal secretion are discussed. That the intestine secretes fluid under physiological conditions is not proven but seems very likely. Several mechanisms seem to be involved in the production of fluid by the intestine. The adenylate-cyclase-cyclic adenosine monophosphate (AMPc) system is currently thought to play a major role in endotoxins and some hormone-induced secretions. The site of intestinal secretion remains a matter of discussion: both crypts and villi seem to participate in the secretory process.

Adenylyl Cyclases↗

PubMed1992

An enzymatic mechanism for potassium channel stimulation through pertussis-toxin-sensitive G proteins.

Many neurotransmitters inhibit secretion from electrically excitable cells by activating pertussis-toxin-sensitive G proteins that modulate voltage-gated ion channels. Recent electrophysiological studies of metabolically intact cells from mammalian and molluscan neuroendocrine systems have implicated protein phosphatases in this process. In this article David Armstrong and Richard White review these studies and suggest a biochemical pathway that might link one of the G proteins to protein phosphatase activity.

Animals↗

PubMed1975

Lymphocyte depletion induced by cholera toxin; relationship to adrenal cortical function.

Intravenous injection of cholera toxin (choleragen) into mice caused a profound lymphocytopenia associated with marked cellular depletion of the lymph nodes, spleen, and thymus. After administration of 1 mu g of choleragen, lymphocytopenia was mot marked at 24 hr; recovery occurred 6 to 10 days later. Similarly depletion of lymph nodes and spleen was maximal at 24 hr with recovery by 14 days. Choleragen also caused a marked elevation of serum corticosterone and lymphocyte depletion was not observed in adrenalectomized mice. These results suggested that the lymphocytopenic effect of choleragen was mediated by increased production and secretion of adrenal cortical hormones secondary to a rise in intracellular cAMP induced by cholera toxin. The site of action of choleragen may be the adrenal cortex itself and/or the hypothalamic-pituitary system.

Adrenal Cortex↗

PubMed2019

Large-scale genome analysis of bovine commensal Escherichia coli reveals that bovine-adapted E. coli lineages are serving as evolutionary sources of the emergence of human intestinal pathogenic strains.

How pathogens evolve their virulence to humans in nature is a scientific issue of great medical and biological importance. Shiga toxin (Stx)-producing Escherichia coli (STEC) and enteropathogenic E. coli (EPEC) are the major foodborne pathogens that can cause hemolytic uremic syndrome and infantile diarrhea, respectively. The locus of enterocyte effacement (LEE)-encoded type 3 secretion system (T3SS) is the major virulence determinant of EPEC and is also possessed by major STEC lineages. Cattle are thought to be the primary reservoir of STEC and EPEC. However, genome sequences of bovine commensal E. coli are limited, and the emerging process of STEC and EPEC is largely unknown. Here, we performed a large-scale genomic comparison of bovine commensal E. coli with human commensal and clinical strains, including EPEC and STEC, at a global level. The analyses identified two distinct lineages, in which bovine and human commensal strains are enriched, respectively, and revealed that STEC and EPEC strains have emerged in multiple sublineages of the bovine-associated lineage. In addition to the bovine-associated lineage-specific genes, including fimbriae, capsule, and nutrition utilization genes, specific virulence gene communities have been accumulated in stx- and LEE-positive strains, respectively, with notable overlaps of community members. Functional associations of these genes probably confer benefits to these E. coli strains in inhabiting and/or adapting to the bovine intestinal environment and drive their evolution to highly virulent human pathogens under the bovine-adapted genetic background. Our data highlight the importance of large-scale genome sequencing of animal strains in the studies of zoonotic pathogens.

Animals↗

PubMed2026

Occurrence of blaOXA-72 in a clinical isolate of carbapenem-resistant Acinetobacter pittii ST206 in Japan.

The development of carbapenem resistance in Acinetobacter spp., which are recognized as significant opportunistic pathogens, is of critical importance as it poses challenges to therapy and the control of healthcare-associated infections in clinical settings. This study investigated the genetic characteristics of a carbapenem-resistant A. pittii clinical isolate from a university hospital using whole-genome sequencing. The A. pittii strain SU8507, which was detected in the abdominal drainage fluid of a patient, exhibited resistance to imipenem (MIC: 128 μg/mL) and meropenem (MIC: 64 μg/mL) and produced positive results by the CIMTris method. A. pittii SU8507, belonging to ST206, harbored the blaOXA-72 and new variants of intrinsic blaOXA-213-like gene blaOXA-1222, which lacks an upstream insertion sequence element, and blaADC-1-like gene blaADC-343. The blaOXA-72 gene, flanked by XerC/XerD-like recombination sites, was located on a plasmid pSU8507, sized at 10,913 bp, carrying 13 predicted protein-coding genes. Complete pSU8507 containing mobA, repB, and the yoeB-yefM toxin-antitoxin genes, showed 98.9% nucleotide sequence identity and 75% coverage with plasmid pA2702 of the A. baylyi strain A2702, but a low BLAST MAX score. SU8507 harbored virulence genes involved in biofilm formation, types II and VI secretion systems, type IV pilus system, and serum resistance. This study describes the first isolation of an OXA-72-producing, carbapenem-resistant A. pittii clinical isolate in Japan. Given that the isolation rate of carbapenem-resistant Acinetobacter spp. Remains low in Japan, it is crucial to expand the scope of rapid, accurate carbapenemase detection to include not only A. baumannii, but also non-baumannii Acinetobacter spp.

Humans↗

PubMedDate not supplied

'Depletion' of ATP by 2-deoxyglucose: secretion by electroporated human neutrophils is not restored by readdition of ATP.

Studies of intracellular signal transduction are facilitated by the use of permeabilized cell systems, which permit the ready manipulation of the cytosol. These model systems have helped to define the roles that small solutes, particularly Ca2+ and nucleotides, play in stimulus-response coupling. In circumstances where the full depletion of intracellular ATP contents is required, some investigators have resorted to prior treatment with metabolic toxins, with the expectation that the role of ATP in signal transduction could then be more unambiguously studied. However, in the work reported here, we found that treatment with 2-deoxyglucose (2-DOG) irreversibly altered the cells: when poisoned human neutrophils were then permeabilized, the cells failed to degranulate well in response to Ca2+, and their sensitivity to Ca2+ could not be recovered by the readdition of ATP. Inhibition of secretion by 2-DOG was most pronounced when low concentrations of Ca2+ were used as the stimulus. Preincubation of the cells with only 1 mM 2-DOG for 10 min at 37 degrees C (prior to washing and permeabilizing the cells) was sufficient for maximal inhibition. Even without preincubation, high concentrations of 2-DOG directly inhibited secretion. The refractory nature of poisoned cells was not restored by the presence of Mg2+ and/or ATP. The protein kinase C agonist phorbol myristate acetate also did not restore sensitivity of secretion to Ca2+. Addition of ATP and/or GTP to the permeabilization medium (to maximize penetration of the nucleotides) failed to restore sensitivity; tracer studies demonstrated that these conditions were adequate for repletion of the nucleotide pool. These data indicate that human neutrophils poisoned with 2-DOG were irreversibly altered, such that restoration of the putative deficiency (ATP) was without effect. Experiments in which such preincubation measures are employed should be viewed with caution.

Adenosine Triphosphate↗

PubMed1992

Comparative effects of atrial natriuretic peptide and E. coli heat-stable toxin on rat intestinal transport.

Conflicting data have been published in favor of or against a secretory effect of atrial natriuretic peptide (ANP) in the intestine. The reported effects resemble that of Escherichia coli heat-stable enterotoxin (ST). In this work the effects of ANP were studied in well established experimental systems and compared with that of ST. Both peptides induced a prompt secretion of water, Na, and Cl with no effects on K net transport in the in vivo rat perfused jejunum. The addition of ST, but not of ANP, evoked an increase of short circuit current in rat intestinal mucosa mounted in Ussing chambers. ST induced a significant increase in guanylate cyclase activity in intestinal homogenates, whereas ANP showed no effect. No binding sites for ANP were detected in basolateral or brush border membranes, nor in isolated enterocytes by a suction filtration technique. In conclusion, ANP acts as a short-lived intestinal secretagogue in the rat. Its mechanism of action is different from that of E. coli ST and appears to be indirect, since is not mediated by specific intestinal receptors and is not evident in vitro.

Animals↗

PubMed1992

Construction and expression of diphtheria toxin-encoding gene derivatives in Escherichia coli.

We reported earlier that in the periplasmic space of Escherichia coli, truncated derivatives of diphtheria toxin undergo limited proteolysis [Zdanovsky et al., Mol. Biol. 22 (1988) 1037-1293]. Here, we present data indicating that this proteolysis is reduced in cells bearing a mutation in the degP gene. We have also constructed hybrid genes whose products are not secreted into the periplasm. These hybrid genes were expressed in E. coli from both the pR promoter, controlled by the heat-inducible CI857 repressor, and from the P(lac) promoter, controlled by the IPTG-inducible LacI repressor. The latter system proved to be more productive.

Bacteriophage lambda↗

PubMedDate not supplied

Toxin resistance and reduced secretion in a mouse L-cell mutant defective in herpes virus propagation.

The mouse L-cell mutant gro29 was selected originally for its inability to propagate herpes simplex virus; it shows severe defects in virus egress and the transport and processing of viral glycoproteins after infection. In this report, we show that uninfected gro29 cells display pleiotropic changes in protein secretion, oligosaccharide processing, and sensitivity to the toxins ricin and modeccin. Specifically, the rate of secretion of a nonglycosylated protein, human growth hormone, was reduced 70% in gro29 cells compared with the parental L cells. A direct measurement of the transport capacity of Golgi membranes in a cell-free assay suggests that gro29 cells contain less functional Golgi than parental cells. Despite this deficiency, N-linked oligosaccharides were processed efficiently in mutant cells, although there were differences in the structure of the mature forms. Lectin intoxication assays revealed that gro29 cells were cross-resistant to killing by the cytotoxic lectins ricin and modeccin, but not to wheat germ agglutinin, Ricinus communis agglutinin RCA120, or leucoagglutinin. Fluorescence labeling using fluorescein-conjugated lectins showed that uninfected gro29 cells expressed relatively few ricin-binding molecules, suggesting a possible mechanism for toxin resistance. These studies provide evidence that the processes of protein secretion, lectin intoxication, and herpes virus maturation and egress may share a common cellular component.

Animals↗

PubMed1975

Pathogenesis of Salmonella-mediated intestinal fluid secretion. Activation of adenylate cyclase and inhibition by indomethacin.

Salmonella typhimurium, an organism that invades intestinal mucosa but does not elaborate a traditional enterotoxin, evokes ileal secretion by causing alterations in active sodium and chloride transport mechanisms. To evaluate the possibility that these changes in transport might be related to the adenylate cyclase-cyclic AMP or NA+-K+-adenosine triphosphatase (ATPase) systems, mucosal adenylate cyclase, cAMP phosphodiesterase, Na+-K+ and Mg++ ATPase activities, and cAMP concentrations were measured in rabbit ileal loops infected with two strains of S. typhimurium. Strain TML invades the mucosa and evokes fluid secretion whereas strain SL 1027 invades but does not evoke secretion. Cholera toxin-stimulated loops were also studied. When compared to control loops, TML-infected mucosa demonstrated a marked increase in adenylate cyclase activity, in cAMP concentration, and no change in phosphodiesterase or ATPase activities. SL 1027-infected mucosa demonstrated no change in either adenylate cyclase or ATPase activities. Indomethacin pretreatment of cyclase activation. In contrast, indomethacin pretreatment of cholera toxin exposed animals resulted in only a partial reduction of secretion while not altering the stimulation of adenylate cyclase. These results suggest that: (1) S. typhimurium causes ileal secretion by stimulating adenylate cyclase; (2) mucosal invasion alone (SL 1027) is not sufficient to activate adenylate cyclase, and (3) Na+-K+-ATPase does not appear to be involved in salmonella-induced secretion. The mechanism of salmonella activation of adenylate cyclase is unclear but apparently differs from that of cholera toxin in that it is inhibited by indomethacin. This might be explained by the participation of prostaglandins in the salmonella activation process.

Adenosine Triphosphatases↗