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At least 19 recordsLinked to original sources
PubMed1988

Interaction of polymyxin B1 and polymyxin B1 nonapeptide with phosphatidic acid monolayer and bilayer membranes.

The interactions of the antibiotic polymyxin B1 and its enzymatic cleavage product polymyxin B1 nonapeptide with phosphatidic acid monolayers and with bilayer membranes were investigated. Temperature-dependent pressure-area analysis of the monolayer reveals a linear increase of the lipid mean molecular area in the liquid condensed state for polymyxin concentrations between 10(-8) and 4 x 10(-7) M. Depending on the surface pressure, the area increase amounts to 30-70 A2. A linear dependence was also observed in the liquid expanded state but saturation is reached already at 10(-7) M polymyxin. The adsorption of polymyxin to phosphatidic acid bilayers is also linear and of a Langmuir type. Saturation is reached at a 1:4 polymyxin/lipid molar ratio. Polymyxin induces a phase separation in phosphatidic acid monolayers which was concluded from the thermotropic phase transition curves. In agreement with earlier bilayer experiments a second lowered phase transition appears in the presence of polymyxin. These fluidized domains again exhibit a linear polymyxin uptake comparable to the one of the liquid expanded monolayer at a temperature, where the undisturbed lipid is still in the condensed state. Polymyxin nonapeptide also causes an expansion of phosphatidic acid monolayers but only by maximally 10 A2. The thermotropic phase transition of the monolayer is reduced and considerably broadened by the nonapeptide. In phosphatidic acid bilayers we observed a decrease of the lipid phase transition temperature by 24 degrees C. The lateral chain packing is considerably disturbed by the peptide part of polymyxin.(ABSTRACT TRUNCATED AT 250 WORDS)

Binding, Competitive↗
PubMed1982

Chemical alterations in cell envelopes of polymyxin-resistant mutants of Pseudomonas aeruginosa grown in the absence or presence of polymyxin.

The polymyxin-resistant mutant strains H181 and H185 of Pseudomonas aeruginosa, after growth in the absence or presence of polymyxin, were compared with the polymyxin-sensitive H103 strain as to their cell envelope protein composition (determined by slab polyacrylamide gel electrophoresis) and their lipid composition. When grown in the absence of polymyxin, the H181 and H185 strains had an increased content of the outer membrane protein H1 with a decreased content of the outer membrane proteins D2 and F. After growth in the presence of polymyxin, the content of H1, D2, and F were all decreased. Significant alterations in the lipid composition of the H181 and H185 strains were found after growth in the absence of polymyxin. These lipid alterations were enhanced upon growth in the presence of polymyxin, with both strains having a reduced content of phosphatidylethanolamine and phosphatidylglycerol and an increased content of diphosphatidylglycerol and an unidentified lipid thought to be a neutral lipid. Other workers have proposed that an increased content of H1 protein is the molecular basis for polymyxin resistance in the H181 and H185 strains. Our observations make this hypothesis appear unlikely.

Bacterial Proteins↗
PubMed1984

Chemical alterations in cell envelopes of Pseudomonas aeruginosa upon exposure to polymyxin: a possible mechanism to explain adaptive resistance to polymyxin.

Polymyxin-susceptible cells of Pseudomonas aeruginosa were exposed for 10, 30, and 60 min to growth medium containing 6000 units of polymyxin per millilitre. Exposure for 10 min resulted in lipid alterations in the cell envelope. A large reduction in the content of both phosphatidylethanolamine and phosphatidylglycerol with a large increase in both diphosphatidylglycerol and free fatty acids was found upon analysis by thin-layer chromatography. The cellular percentage of readily extractable lipid (REL) was reduced, and the phospholipid proportion of the REL decreased with polymyxin exposure. Polymyxin exposure for 30 and 60 min only slightly enhanced these chemical alterations. The cell envelope alterations found were characteristic for strains which become adaptively resistant to polymyxin. Treatment of the cells with chloramphenicol or KCN prior to polymyxin exposure did not prevent the lipid alterations from occurring. These observations suggest that the polymyxin-susceptible cell population adapts to polymyxin resistance by the rapid alteration of the cell envelopes of the entire cell population. We propose the theory that cell envelope phospholipases and proteases play a major role in the adaptive response and that the cation content of the cell envelope may be a critical controlling factor in the process.

Cell Membrane↗
PubMed1976

Combinations of antimicrobial agents: II. The in vitro sensitivity of 52 strains of proteus species to sulphafurazole, polymyxins and combinations of sulphafurazole and polymyxins.

The sensitivity of 52 strains of Proteus species to sulphafurazole, polymyxins and the combinations of sulphafurazole and polymyxins was determined by means of discs and trays. It was found that 2 and 6 strains, respectively, were sensitive to discs containing 100 mug sulphafurazole and 300 mug polymyxin B, respectively, 41 strains were sensitive to the combination of discs containing 100 mug sulphafurazole and 50 mug colistin, respectively, and 38 strains were sensitive to the combination of discs containing 100 mug sulphafurazole and 300 mug polymyxin B, respectively. The tray method proved that 2 and 5 strains were sensitive to 25 and 200 mug sulphafurazole, respectively, and that 1, 2 and 3 strains were sensitive to 25, 50 and 100 mug polymyxin B, respectively. Also 41 strains were sensitive to the combination of 100 mug sulphafurazole and 25 mug colistin and 38 strains were sensitive to the combination of 25 mug sulphafurazole and 6.3 mug polymyxin B. There was good agreement between the results of the disc and of the tray studies. The synergism between sulphonamides and polymyxins may offer therapeutic possibilities.

Drug Synergism↗
PubMed1983

Trimethoprim-polymyxin B ophthalmic solution in the treatment of presumptive bacterial conjunctivitis--a multicentre trial of its efficacy versus neomycin-polymyxin B-gramicidin and chloramphenicol ophthalmic solutions.

Two-hundred and thirty patients with a diagnosis of presumptive bacterial conjunctivitis were assessed in a randomized double-blind multicentre trial. In two of the centres the patients had been treated with either trimethoprim-polymyxin B or neomycin-polymyxin B-gramicidin ophthalmic solution. In the other two centres the patients had been treated with either trimethoprim-polymyxin B or chloramphenicol ophthalmic solution. All of the preparations used were shown to be effective and very few adverse reactions were encountered. No significant difference in clinical efficacy could be demonstrated between trimethoprim-polymyxin B and neomycin-polymyxin B -gramicidin but trimethoprim-polymyxin B was found to be significantly better (P = 0.03) than chloramphenicol in reducing signs and symptoms.

Chloramphenicol↗
PubMed1989

Fatty acid alterations and polymyxin B binding by lipopolysaccharides from Pseudomonas aeruginosa adapted to polymyxin B resistance.

Lipopolysaccharides were extracted from freeze-dried cells of Pseudomonas aeruginosa PAO1 (polymyxin B susceptible), isolate A (polymyxin B resistant), and isolate A-reverted (polymyxin B intermediate resistance) by either the phenol-chloroform-petroleum ether or the modified phenol-water method. Isolate A and isolate A-reverted had drastic losses of 2-hydroxydodecanoic acid and significant decreases in 3-hydroxydecanoic acid. Concentrations of amide-linked 3-hydroxydecanoic acid were similar in all three strains. Minor alterations were noted in the composition of 3-deoxy-D-manno-2-octulosonic acid, heptose, phosphate, neutral sugars, and amino compounds. The concentrations of rhamnose in isolate A and of rhamnose and glucose in isolate A-reverted were significantly different from those in PAO1. Trace amounts of mannose and other minor unidentified carbohydrates were detected in all strains. Polymyxin B included in isolate. A growth medium complexed with lipopolysaccharides and remained bound throughout purification. PAO1 lipopolysaccharides bound more polymyxin B than did isolate A lipopolysaccharides. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicated minor differences in smooth- and rough-form lipopolysaccharides of the different strains. We propose that loss of hydroxy fatty acids from lipopolysaccharides perturbs outer membrane hydrophobicity and is a contributing factor to polymyxin B adaptive resistance.

Drug Resistance, Microbial↗
PubMed1991

[Structure-functional studies of polymyxins. (1)-NMR analysis of polymyxin B and M conformation].

Spatial structures of two polymyxin antibiotics are compared by means of one- and two-dimensional 1H NMR spectroscopy. Cyclic parts of polymyxins B and M contain a system of hydrogen bonds including two beta-turns, however, the analysis of coupling constants 3JHN-C alpha H demonstrated that torsional angles phi of peptide bonds of the residues forming beta-turns in polymyxin M depend on the type of the anion. An increase in lability of the polymyxin M cyclic part in comparison with polymyxin B correlated with the selective cleavage of the peptide bond Dab8-Dab9 of this antibiotic with subtilisin. A similar correlation was found for a short analogue of polymyxin B, a cycloheptapeptide.

Magnetic Resonance Spectroscopy↗
PubMed1993

Quantitative analysis of polymyxin B released from polymyxin B-treated dormant spores of Bacillus subtilis and relationship between its permeability and inhibitory effect on outgrowth.

Polymyxin B, one of the cyclic polypeptide antibiotics, binds to the coat of Bacillus subtilis dormant spores and inhibits them from growing after germination. When about 2.8 x 10(8) cells/ml of polymyxin B-treated dormant spores were incubated in heart infusion broth, 3.6 micrograms/ml of polymyxin B were released into the liquid medium during germination. Incubation of the same concentration of polymyxin B-treated ones in 100 mM CaCl2 solution released 4.0 micrograms/ml of the antibiotic. The effect of various concentrations of polymyxin B on germination, outgrowth and vegetative growth of the dormant spores was investigated; the results showed that concentrations of 4.0 micrograms/ml and higher of the antibiotic inhibited their outgrowth and vegetative growth after germination. Young vegetative cells were less sensitive to the antibiotic than germinated spores. In addition to these results, immunoelectron microscopy with colloidal gold particles indicated that polymyxin B permeated into the core of the germinated spores and inhibited them from outgrowing.

Bacillus subtilis↗
PubMed1981

Outer membrane permeability barrier disruption by polymyxin in polymyxin-susceptible and -resistant Salmonella typhimurium.

In contrast to their polymyxin-susceptible parent strains, polymyxin-resistant Salmonella typhimurium mutants (pmrA strains) did not lose their outer membrane permeability barrier to macromolecules such as lysozyme and periplasmic proteins upon polymyxin treatment. The sensitization of pmrA strains to deoxycholate-induced lysis required 10-times-higher polymyxin concentrations than did the sensitization of the parent strains. These findings indicate that the pmrA mutation affects the outer membrane and decreases its susceptibility to polymyxin. By contrast, the pmrA mutants did not differ from their parents in the uptake of gentian violet after treatment with polymyxin, suggesting a degree of specificity in the pmrA effect in the outer membrane.

Bacterial Proteins↗
PubMed1986

Polymyxin B and polymyxin B nonapeptide alter cytoplasmic membrane permeability in Escherichia coli.

The effects of polymyxin B and polymyxin B nonapeptide (PMBN) on the permeability of the Escherichia coli cytoplasmic membrane were investigated. Both compounds caused loss of free amino acids, uracil and K+ from E. coli. The rates of loss promoted by polymyxin B were one and a half to two-fold greater than those caused by PMBN. Although PMBN mediated loss of low molecular weight substances from E. coli, it was not bactericidal. In contrast, polymyxin B treated E. coli lysed and rapidly lost viability. We suggest that the bactericidal activity of polymyxin B may be related to its previously reported ability to release cytoplasmic proteins from bacteria.

Amino Acids↗
PubMed1976

Action of polymyxin B on bacterial membranes. Binding capacities for polymyxin B of inner and outer membranes isolated from Salmonella typhimurium G30.

Radioactive mono-N-acetyl-14C-polymyxin B or natural polymyxin B are within 60 s absorbed by isolated inner (cytoplasmic) and outer membranes from Salmonella typhimuriumG30. The sigmoidal binding isotherms indicate saturation of inner and outer membranes with approximately 30 and 60 nmoles polymyxin B bound per mg membrane, respectively. Based on the known content of these membranes in lipopolysaccharide, phosphatidylglycerol, cardiolipin and phosphatidylethanolamine, a calculation of the theoretical binding capacities yields almost identical values if lipopolysaccharide, phosphatidylglycerol and cardiolipin are assumed to function as the actual binding sites for the antibiotic in the isolated membranes. The excellent agreement between theoretical evaluation and experimental determination of polymyxin B-binding capacities leaves little doubt that the named anionic compounds are the chemoreceptors for the cationic antibiotic. This is further substantiated by very similar binding and killing kinetics of polymyxin B.

Binding Sites↗
PubMed1976

Action of polymyxin B on bacterial membranes: phosphatidylglycerol- and cardiolipin-induced susceptibility to polymyxin B in Acholeplasma laidlawii B.

To identify the polymyxin receptor molecules in the membranes of living microorganisms, fusion of intact Acholeplasma laidlawii B with lipid vesicles was investigated according to the procedure of Grant and McConnell (1973). The naturally polymyxin-resistant A. laidlawii B was treated with phospholipid vesicles prepared from purified phospholipids of the polymyxin-susceptible Salmonella typhimurium G30. A. laidlawii B absorbed between 15 and 45% of its own lipid content of the added tritium-labeled phospholipids without loss of viability. Association with the acidic components phosphatidylglycerol and cardiolipin produced a 10- to 30-fold increase in polymyxin susceptibility, which was not obtained with egg-phosphatidylcholine and mixed phosphatidylcholine-phosphatidylethanolamine vesicles. The polymyxin-sensitized cells bound 12 times more radioactive antibiotic than resistant cells. The phosphatidylglycerol-induced susceptibility was abolished by serum fraction V (Cohn) proteins.

Acholeplasma laidlawii↗
PubMed1976

Effect of polymyxin on the ultrastructure of the outer membrane of wild-type and polymyxin-resistant strain of Salmonella.

The effect of polymyxin on two sets of Salmonella mutants was studied by thin-section and scanning electron microscopy. Polymyxin (in increasing concentrations, starting just below bactericidal effect) caused the appearance of the previously described rodlike projections on the cell surface of wild-type (smooth, polymyxin-sensitive) bacteria. These projections seemed to involve the outer membrane of the cell wall. In rough mutants, which are deficient in lipopolysaccharide, the projections were much smaller and flat. Higher concentrations of polymyxin were required to produce morphological effects in polyxmin-resistant mutants of both smooth and rough forms. Furthermore, in these mutants polymyxin caused vesicle-like bulging of the total outer membrane quite different in appearance from the rodlike projections of the wild type.

Cell Membrane↗
PubMed1985

Effects of polymyxin B sulfate and polymyxin B nonapeptide on growth and permeability of the yeast Saccharomyces cerevisiae.

Polymyxin B, a toxic, membrane-affecting antibiotic, can be rendered harmless to yeast cells by enzymatic removal of its fatty acyl moiety. The remaining cyclic peptide portion, polymyxin B nonapeptide, has no significant effect on growth and viability but it drastically reduces mating efficiency. In addition, the cyclic peptide enhances sensitivity of cells to several drugs, presumably by increasing membrane permeability. Mutants resistant to polymyxin B are simultaneously less responsive to the combination of the nonapeptide and the drugs. This indicates that the peptide portion of polymyxin B is the moiety responsible for the permeability changes. The resistance is inherited as a simple recessive trait. The mutation has been mapped to chromosome XV of Saccharomyces cerevisiae.

Anti-Bacterial Agents↗
PubMed1987

Polymyxin B binding sites in Escherichia coli as revealed by polymyxin B-gold labeling.

A complex of polymyxin B, bovine serum albumin, and colloidal gold was prepared and used for the ultrastructural localization of polymyxin B binding sites on thin sections of Epon-embedded Escherichia coli cells. Gold particles were found on the outer membrane of E. coli, which is consistent with reported biochemical findings. We concluded that gold labeling with polymyxin B is useful in localizing the binding sites of polymyxin.

Binding Sites↗
PubMed1987

[Structural and functional research on polymyxins. 1H NMR analysis of the conformation of polymyxin M in water].

Spatial structure of polypeptide antibiotic polymyxin M in water was studied by one-and two-dimensional (COSY, COSY-45, RELAY) H NMR spectroscopy. Analysis of the signal spectral parameters revealed two intramolecular hydrogen bonds in the cyclic part of the molecule which was analogous to the structure of polymyxin B. However, configuration of both the beta-turns in the polymyxin M structure differed from that of the detected earlier beta-turns in the structure of polymyxin B.

Hydrogen↗
PubMed1976

Combinations of antimicrobial agents. III. The in vitro sensitivity of 12 strains of Pseudomonas aeruginosa and 12 strains of proteus species ot sulphamethoxazole + trimethoprim (co-trimoxazole), polymyxins and combinations of co-trimoxazole and polymyxins.

The sensitivity of 12 strains of Pseudomonas aeruginosa and of 12 strains of Proteus species to co-trimoxazole, polymyxins and combinations of co-trimoxazole and polymyxins was determined by disc and tray methods. It was found that all strains were sensitive to the combinations of co-trimoxazole and polymyxins. The disc study of the strains of Ps. aeruginosa revealed a typical image with many strains. The tray study gave a typical image with two strains of Proteus species. The two images are briefly discussed. The synergistic action of co-trimoxazole and polymyxins may well offer therapeutic possibilities.

Drug Combinations↗