Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.4.3 (phospholipase C)
 18,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We examined the effects of subinhibitory concentrations of ciprofloxacin, tobramycin, and ceftazidime on Pseudomonas aeruginosa exoenzyme expression in vitro and in vivo. Exotoxin A, exoenzyme S, phospholipase C, elastase, and total protease activities were suppressed by antibiotics at concentrations as low as 1/20 of the MIC over a 24-h period in broth. Continuous 10-day exposure of P. aeruginosa DG1 broth cultures to antibiotic levels equal to 1/10 of the MIC reduced exoenzyme S activity in all treatment groups. Elastase activity was reduced only by ciprofloxacin and tobramycin treatment. This suppressive effect of the antibiotics persisted throughout the 10 days and was not influenced by the increase in MIC of ciprofloxacin detected during the course of the experiment. Rats chronically infected with P. aeruginosa were treated with subinhibitory doses of antibiotics and compared with untreated controls. Bacterial numbers in lung homogenates from each of the four study groups were identical. However, the lungs from antibiotic-treated rats had significantly less histological damage than those from control rats (P less than 0.001). The protective effect was greatest for ciprofloxacin and tobramycin. Further, P. aeruginosa isolates from ciprofloxacin- and tobramycin-treated rats demonstrated significantly less exoenzyme S and elastase activity than isolates from untreated rats (P less than 0.001). Isolates from ceftazidime-treated lungs expressed less exoenzyme S activity (P less than 0.001) but an equivalent amount of elastase activity as isolates from controls. The suppression of P. aeruginosa exoenzymes may arrest progressive lung injury during chronic P. aeruginosa lung infections.
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PMID:Inhibition of Pseudomonas aeruginosa exoenzyme expression by subinhibitory antibiotic concentrations. 249 57

We have recently reported (D.L. Stevens, K.A. Maier, B.M. Laine, and J.E. Mitten, J. Infect. Dis. 155:220-228, 1987) that clindamycin, rifampin, and tetracycline were more efficacious than penicillin in the treatment of fulminant gas gangrene in mice caused by Clostridium perfringens. We hypothesize that antibiotic efficacy correlated with bactericidal or toxin-suppressing properties of these agents. To investigate the possibility that penicillin is only bacteriostatic against C. perfringens, we performed macrobroth dilution MIC and MBC determinations using C. perfringens ATCC 13124. Mean MICs were equal to MBCs for the following antibiotics (micrograms per milliliter): clindamycin, 0.07; tetracycline, 0.05; rifampin, 0.03; metronidazole, 0.69; and penicillin, 0.27. The MIC/MBCs of chloramphenicol were 1.50/3.10 (micrograms/ml). Because antibiotic efficacy did not correlate with bactericidal activity, we measured alpha-toxin activity and found complete suppression of alpha-toxin activity by tetracycline, metronidazole, rifampin, clindamycin, and chloramphenicol at concentrations equal to the MIC. In contrast, alpha-toxin activity persisted at concentrations of penicillin equal to and above the MIC. The dynamics of bacterial killing and kinetics of alpha-toxin production were next studied in log-phase cultures of C. perfringens with antibiotic concentrations 10 times the MIC. Clindamycin, metronidazole, and rifampin all caused rapid reductions in viability, turbidity, and alpha-toxin activity by 15 to 45 min. In contrast, penicillin demonstrated slower bacterial killing, increased turbidity (62.6% of control), and persistent alpha-toxin activity (80% of control values) for 2 h. Tetracycline and chloramphenicol were the least effective in reducing viability; however, the turbidity of cultures did not increase, and alpha-toxin activity was not detectable. Toxin suppression and rapid bacterial killing may in part explain the observed superior therapeutic efficacy of clindamycin, rifampin, and metronidazole compared with penicillin in the treatment of experimental gas gangrene.
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PMID:Effect of antibiotics on toxin production and viability of Clostridium perfringens. 288 31

Pseudomonas aeruginosa blebs-off membrane vesicles (MVs) into culture medium during normal growth. Release of these vesicles increased approximately threefold after exposure of the organism to four times the MIC of gentamicin. Natural and gentamicin-induced membrane vesicles (n-MVs and g-MVs and g-MVs, respectively) were isolated by filtration and differential centrifugation, and several of their biological activities were characterized. Electron microscopy of both n-MVs and g-MVs revealed that they were spherical bilayer MVs with a diameter of 50 to 150 nm. Immunoelectron microscopy and Western blot (immunoblot) analysis of the vesicles demonstrated the presence of B-band lipopolysaccharide (LPS), with a slightly higher proportion of B-band LPS in g-MVs than in n-MVs. A-band LPS was occasionally detected in g-MVs but not in n-MVs. In addition to LPS, several enzymes, such as phospholipase C, protease, hemolysin, and alkaline phosphatase, which are known to contribute to the pathogenicity of Pseudomonas infections were found to be present in both vesicle types. Both types of vesicles contained DNA, with a significantly higher content in g-MVs. These vesicles could thus play an important role in genetic transformation and disease by serving as a transport vehicle for DNA and virulence factors and are presumably involved in septic shock.
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PMID:Virulence factors are released from Pseudomonas aeruginosa in association with membrane vesicles during normal growth and exposure to gentamicin: a novel mechanism of enzyme secretion. 760 73

The effects of subinhibitory concentrations (1/4, 1/8, 1/16 of the MIC) of 12 organic ammonium salts of A (hard-alkyltrimethylammonium bromides) and B (soft--2-(dodecanoylamino)ethylalkyldimethylammonium bromides) homologous series on phospholipase C, proteinase, elastase and permeability activity were studied. The substances with longer substituents were more effective in reducing phospholipase C activity (hard and soft series) as well as proteinase (hard series). Phospholipase C was the most frequently and the most markedly inhibited enzyme. The organic ammonium salts were less effective in inhibiting elastase and permeability activity. Only one of the substances under study reduced all the tested activities.
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PMID:Enzymic and permeability activity of Pseudomonas aeruginosa after treatment with sub-MICs of organic ammonium salts. 799 1

Aminoglycoside antibiotics, most effective at the level of 1/4 of the MIC, suppressed all the tested activities of P. aeruginosa, except cytotoxicity. Proteinase activity was decreased to 60% (gentamicin) and 63% (streptomycin), permeability was reduced to 61% (gentamicin) and 73% (streptomycin), phospholipase C to 13% (gentamicin) and 51% (streptomycin) of the control values. Subinhibitory concentrations of beta-lactams inhibited only phospholipase C activity to 89% (ticarcillin) and 64% (cefotaxim) of the control values. These antibiotics did not suppress the cytotoxic activity and increased protease activity up to 155% (ticarcillin) and 192% (cefotaxim) as well as permeability up to 121% (ticarcillin) and 154% (cefotaxim) of the control values.
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PMID:Alterations in Pseudomonas aeruginosa exoproducts by sub-MICs of some antibiotics. 811 96

The authors investigated the effect of subinhibitory concentrations (sub-MICs) of selected quinolones (enoxacine, nalidixic acid, norfloxacine) and macrolid antibiotics (erythromycin, roxitromycin) on the production of thermolabile haemolysin (phospholipase C) of P. aeruginosa. The activity of phospholipase C was markedly reduced by norfloxacine (more than 80%) and enoxacine (75 - 80%) in all sub-MICs. Nalidixic acid inhibited phospholipase C in 1/4 of MIC (75%). As to macrolid antibiotics the greatest inhibition was caused by erthromycin in 1/4 and 1/8 MIC (more than 90%). 1/16 MIC of roxitromycin did not influence the activity of the investigated enzyme and other tested sub-MICs caused its reduction to cca one half.
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PMID:[The effect of subinhibitory concentrations of quinolone and macrolide antibiotics on production of thermolabile hemolysins in Pseudomonas aeruginosa]. 855 45

The effects of brodimoprim, a new trimethoprim analogue, on several virulence traits of respiratory and urinary tract pathogens exposed to sub-lethal levels of the drug was studied. Adherence to tracheal epithelial cells was inhibited by brodimoprim in Klebsiella pneumoniae (41-67% reduction), Moraxella catarrhalis (87-90%) and Haemophilus influenzae (0-53%), while in Streptococcus pneumoniae binding was unaffected. With buccal epithelial cells the comparison between treated and control bacteria indicated statistically significant reduction in adherence with both S.pneumoniae and H.influenzae, (P < 0.015). With M.catarrhalis and Streptococcus pyogenes only marginal changes were detected (P > 0.05). Exoenzyme and capsule production were assessed in at least three isolates of diverse respiratory pathogens grown in the presence of sub-lethal levels of the new agent. The drug affected protease and beta-hemolysin (alpha-toxin) production in both oxacillin-susceptible and -resistant S.aureus. On the contrary, synthesis of lipase, DNase, coagulase, and beta-lactamase (S.aureus), pneumolysin (S.pneumoniae), streptolysin S, DNase, and protease (S.pyogenes), capsule (K.pneumoniae, H.influenzae and S.pneumoniae), and beta-lactamase (K.pneumoniae, H.influenzae and M.catarrhalis) were not inhibited by subminimal inhibitory concentrations (sub-MICs) of the drug. Finally, motility was blocked in urinary pathogens E.coli, P.mirabilis and P.aeruginosa, while in this latter microorganism pigment production was also affected. High molecular weight low-copy F'lac, and low molecular weight high-copy pHSG298 plasmids were eliminated from E.coli treated with sub-MIC concentrations of brodimoprim. The incidence and cured cells ranged from 9% for F'lac to 23% for pHSG298. F'lac transfer was also inhibited by the drug. When conjugation was carried out with bacteria exposed to brodimoprim (5XMIC), a reduction (50%) in the number of recombinants was noted in comparison to the control. The fact that brodimoprim interferes with the expression of some virulence traits, in particular with adherence, at sub-MIC levels may assist the drug in eradicating respiratory pathogens from the epithelial lining, thus diminishing the probability of reinfection.
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PMID:Brodimoprim: effects of subminimal inhibitory concentrations on virulence traits of respiratory and urinary tract pathogens, and on plasmid transfer and stability. 880 12

We have studied the postantibiotic effect (PAE) and postantibiotic sub-MICs effect (PA SME) of ciprofloxacin, pefloxacin, netilmicin and tobramycin on the production of phospholipase C (PLC) in a Pseudomonas aeruginosa strain isolated from clinical material. All antibiotics tested (postantibiotic phase evoked by 2.MIC) reduced the production of PLC, particularly pefloxacin to 13.2%. The PA phase evoked by 4.MIC of quinolones did not cause regrowth of P. aeruginosa and aminoglycosides inhibited PLC, in particular with tobramycin to 16.9%. The effect of PA SME (2.MIC) of netilmicin and tobramycin inhibited PLC more expressively (< 20%) than ciprofloxacin; pefloxacin did not allow regrowth. PA SMEs of the antibiotics tested reduced the production of PLC more effectively than PAE.
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PMID:The influence of postantibiotic effects and postantibiotic effects of sub-inhibitory concentrations of quinolones and aminoglycosides on phospholipase C of Pseudomonas aeruginosa. 912 76

The in vitro postantibiotic effect (PAE) and the postantibiotic effect of subinhibitory concentrations (PA SME) of gentamicin were investigated on clinical isolates of Salmonella typhimurium, Salmonella enteritidis and Pseudomonas aeruginosa. The PAE was induced by 2 x MIC and 4 x MIC of gentamicin for 0.5 h. The PA SME were studied by the addition of 0.1, 0.2 and 0.3 x MIC during the postantibiotic phase of the bacteria. The S. enteritidis strain did no regrow after affecting of supra-subinhibitory concentrations for 24 h with exception of the concentration 2 x MIC + 0.1 x MIC. The PAEs against P. aeruginosa were nearly identical for all the suprainhibitory concentrations tested (4.4-4.6 h) and no regrowth after PA SME was observed. The studied pharmacodynamic parameters decreased the surface hydrophobicity of Salmonella sp., mainly of S. enteritidis, evaluated by the ability to bind Congo red and by the aggregation in solutions of ammonium sulphate (SAT). Gentamicin in suprainhibitory concentrations expressively decreased the phospholipase C production--an important virulence factor of P. aeruginosa.
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PMID:Pharmacodynamic parameters of gentamicin and their effect on biological properties of gram-negative bacteria. 947 60

Concentrations of antibiotics below the MIC are able to modulate the expression of virulence-associated genes. In this study, the influence of subinhibitory doses of 31 antibiotics on the expression of the gene encoding the staphylococcal alpha-toxin (hla), a major virulence factor of Staphylococcus aureus, was investigated with a novel gene fusion protocol. The most striking observation was a strong induction of hla expression by subinhibitory concentrations of beta-lactams and an almost complete inhibition of alpha-toxin expression by clindamycin. Whereas glycopeptide antibiotics had no effect, the macrolide erythromycin and several aminoglycosides reduced and fluoroquinolones slightly stimulated hla expression. Furthermore, Northern blot analysis of hla mRNA and Western blot (immunoblot) analysis of culture supernatants of both methicillin-sensitive and methicillin-resistant S. aureus strains revealed that methicillin-induced alpha-toxin expression is a common phenomenon of alpha-toxin-producing strains. Some methicillin-resistant S. aureus isolates produced up to 30-fold more alpha-toxin in the presence of 10 microg of methicillin per ml than in its absence. The results indicate that the novel gene fusion technique is a useful tool for studying the modulation of virulence gene expression by antibiotics. Moreover, the results suggest that the effects of certain antibiotics on virulence properties may be relevant for the management of S. aureus infections.
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PMID:Effects of subinhibitory concentrations of antibiotics on alpha-toxin (hla) gene expression of methicillin-sensitive and methicillin-resistant Staphylococcus aureus isolates. 979 9


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