Evidence for two distinct mechanisms of resistance to polymyxin B in Pseudomonas aeruginosa.
AuthorsMoore RA, Chan L, Hancock RE
JournalAntimicrob Agents Chemother
PubMed ID6097168
'Pseudomonas aeruginosa H181 and H185 are resistant to initial exposure to polymyxin B and continue to grow in its presence. Growth of the strains in the presence of 50 U of polymyxin B per ml was characterized by a doubling time of 120 min, whereas the doubling time in the ... More
Interaction of cationic peptides with lipoteichoic acid and gram-positive bacteria.
AuthorsScott MG, Gold MR, Hancock RE
JournalInfect Immun
PubMed ID10569762
'Compounds with antiendotoxin properties have been extensively studied for their potential as therapeutic agents for sepsis attributable to gram-negative bacteria. However, with the increasing incidence of gram-positive sepsis, there is interest in identifying compounds with a broad spectrum of action against both gram-positive and gram-negative bacteria. A series of synthetic ... More
Interaction of cationic peptides with bacterial membranes.
AuthorsFidai S, Farmer SW, Hancock RE
JournalMethods Mol Biol
PubMed ID9276305
Structure--activity relationships of polymyxin antibiotics.
AuthorsVelkov T, Thompson PE, Nation RL, Li J,
JournalJ Med Chem
PubMed ID19874036
Polymyxins are increasingly being used as last-line therapy to treat infections caused by Gram negative bacteria that are resistant to essentially all other currently available antibiotics. We review the current understanding of the mechanisms of microbiologicalactivity and bacterial resistance. The synthesis of polymyxinsis next reviewed, followed by a comprehensive ... More
Anionic lipid domains: correlation with functional topography in a mammalian cell membrane.
AuthorsBearer EL, Friend DS
JournalProc Natl Acad Sci U S A
PubMed ID6935671
Polymyxin B was used to explore distribution of anionic phospholipids in sperm plasma membranes by electron microscopy of freeze-fracture replicas. After exposure to Hepes/Tris-buffered polymyxin at 4 mM, phosphatidylcholine liposomes showed no perturbations nor did they fluoresce with dansylated incubation. When phosphatidylethanolamine was included in the liposomes, they became perturbed ... More
Action of polymyxin B on bacterial membranes: morphological changes in the cytoplasm and in the outer membrane of Salmonella typhimurium and Escherichia coli B.
AuthorsSchindler PR, Teuber M
JournalAntimicrob Agents Chemother
PubMed ID169730
Though the primary action of the cationic antibiotic polymyxin B is against the membrane of susceptible bacteria, severe morphological changes are detected in the cytoplasm. Using fluorescence microscopy and a mono-N-dansyl-polymyxin B derivative, we could demonstrate aggregations of the antibiotic with cellular material, possibly nucleic acids and/or ribosomes. These aggregations ... More
Involvement of outer membrane of Pseudomonas cepacia in aminoglycoside and polymyxin resistance.
AuthorsMoore RA, Hancock RE
JournalAntimicrob Agents Chemother
PubMed ID3028253
Pseudomonas cepacia was found to be resistant to the outer membrane-permeabilizing effects of aminoglycoside antibiotics, polymyxin B, and EDTA. Permeabilization of P. cepacia to the fluorescent probe 1-N-phenylnaphthylamine was not achieved at concentrations 100- to 1,000-fold above those required to permeabilize Pseudomonas aeruginosa. Furthermore, in contrast to P. aeruginosa cells, ... More
Interaction of polycationic antibiotics with Pseudomonas aeruginosa lipopolysaccharide and lipid A studied by using dansyl-polymyxin.
AuthorsMoore RA, Bates NC, Hancock RE
JournalAntimicrob Agents Chemother
PubMed ID3013085
A fluorescent derivative of polymyxin B (dansyl-polymyxin) was used to study the interaction of polycations with lipopolysaccharide (LPS) and lipid A from Pseudomonas aeruginosa. Dansyl-polymyxin became bound to LPS and lipid A sites, including Mg2+-binding sites, resulting in a 20-fold enhancement of fluorescence. A Hill plot of the binding data ... More
Enhanced binding of polycationic antibiotics to lipopolysaccharide from an aminoglycoside-supersusceptible, tolA mutant strain of Pseudomonas aeruginosa.
AuthorsRivera M, Hancock RE, Sawyer JG, Haug A, McGroarty EJ
JournalAntimicrob Agents Chemother
PubMed ID3134845
The lipopolysaccharide (LPS) of the aminoglycoside-supersusceptible Pseudomonas aeruginosa tolA mutant PAO1715 was compared with its parent strain PAO1670 and tol+ revertant PAO1716. Electrophoretic separation of purified LPSs from the three isolates showed similar LPS banding patterns. Analysis of the Western blots of these LPSs from the three isolates with O-antigen-specific ... More
Alterations of phospholipid asymmetry in the membrane of spontaneously aggregated platelets in diabetes.
AuthorsLupu F, Calb M, Fixman A
JournalThromb Res
PubMed ID3413722
The changes of asymmetric distribution of anionic phospholipids of human platelets in diabetic patients were studied by fluorescent and freeze fracture cytochemistry, using merocyanine 540 (MC 540) and polymyxin B (PxB) as specific markers. The membrane anionic phospholipids were detected with PxB, a membrane nonpermeant probe, used either in native ... More