In vitro activity of polyunsaturated fatty acids on Pseudomonas aeruginosa: relationship to lipid peroxidation.
Based on previous findings that gamma-linolenic acid (GLA) inhibits Escherichia coli growth and provokes the induction of strains resistant to aminoglycosides, 19 Pseudomonas aeruginosa strains were exposed in vitro over time to GLA, to arachidonic acid (AA) and to their combination in the presence or absence of vitamin E. All acids were used at a 300 microg/ml concentration, whereas vitamin E was added as an antioxidant. Lipid peroxidation was evaluated by the thiobarbiturate assay measuring malonodialdehyde (MDA) production. It was found that GLA or AA killed 5-10% of strains at 24 h of growth, whereas when applied in combination their effect involved 100% of strains at 24 h and was limited to 68% of strains in the presence of vitamin E (P< 0.01). MDA production was time-dependent and it was restrained by vitamin E (P < 0.01). Post acid exposure, 27% to 37% of the survived strains became resistant to diverse antimicrobial agents and mainly to ticarcillin, to ceftazidime and to amikacin; no strain developed resistance in the presence of vitamin E. It is concluded that GLA and AA interact bactericidally on P. aeruginosa isolates, inducing the development of strains resistant to beta-lactams and to aminoglycosides; their action might be mediated through their peroxides. Further research is necessary to establish the clinical application of these in vitro findings.
Giamarellos-Bourboulis
E J
EJ
1st Department of Propedeutic Medicine, Athens Medical School, Greece.
Grecka
P
P
Dionyssiou-Asteriou
A
A
Giamarellou
H
H
D000583:Amikacin / Q000494:pharmacology; D000668:Ampicillin Resistance; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D016718:Arachidonic Acid / Q000494:pharmacology; D002442:Ceftazidime / Q000494:pharmacology; D018550:Cephalosporin Resistance; D002511:Cephalosporins / Q000494:pharmacology; D015169:Colony Count, Microbial; D004352:Drug Resistance, Microbial; D018432:Drug Resistance, Multiple; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D005839:Gentamicins / Q000494:pharmacology; D015378:Imipenem / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects; D008315:Malondialdehyde / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D010403:Penicillin Resistance; D010406:Penicillins / Q000494:pharmacology; D010878:Piperacillin / Q000494:pharmacology; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D013045:Species Specificity; D013845:Thienamycins / Q000494:pharmacology; D013982:Ticarcillin / Q000494:pharmacology; D014031:Tobramycin / Q000494:pharmacology; D014810:Vitamin E / Q000494:pharmacology; D017965:gamma-Linolenic Acid / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D005231:Fatty Acids, Unsaturated; D005839:Gentamicins; D010406:Penicillins; D013845:Thienamycins; D014810:Vitamin E; D016718:Arachidonic Acid; D008315:Malondialdehyde; D015378:Imipenem; D017965:gamma-Linolenic Acid; D000583:Amikacin; D002442:Ceftazidime; D013982:Ticarcillin; D014031:Tobramycin; D010878:Piperacillin