Adaptive resistance to aminoglycoside antibiotics in Pseudomonas aeruginosa.
Aminoglycoside-resistant variants of Pseudomonas aeruginosa strain PAO1 were readily selected by culturing the organism in medium containing increasing concentrations of gentamicin, tobramycin or amikacin until the strains were growing in a concentration of drug 128-fold greater than the minimal inhibitory concentration for the sensitive parent strain. These resistant strains exhibited characteristics previously associated with the impermeability type of resistance mechanism, i.e., they grew more slowly than the parent strain, the resistance was unstable in the absence of the antibiotic, and adaptation to one of the antibiotics conferred cross-resistance to other aminoglycosides. The adapted strains grew, with minimal morphological alterations, in concentrations of the various aminoglycosides that normally produced cell envelope damage, misshapen and filamentous cell formation, and cell lysis in the sensitive strain. Neither protein H1 nor phospholipid alterations appear to play a significant role in adaptive resistance to aminoglycoside antibiotics in this model system. The acquisition of adaptive resistance to the aminoglycoside antibiotics did not confer resistance to polymyxin B, another cationic antibiotic which is thought to share binding sites within the outer membrane with the aminoglycosides.
Gilleland
L B
LB
Department of Microbiology and Immunology, Louisiana State University Medical Center, School of Medicine, Shreveport 71130.
Gilleland
H E
HE
Gibson
J A
JA
Champlin
F R
FR
D000222:Adaptation, Physiological; D000583:Amikacin / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001425:Bacterial Outer Membrane Proteins / Q000032:analysis; D004352:Drug Resistance, Microbial; D005839:Gentamicins / Q000494:pharmacology; D008055:Lipids / Q000032:analysis; D008854:Microscopy, Electron; D010715:Phosphatidylglycerols / Q000032:analysis; D011550:Pseudomonas aeruginosa / Q000032:analysis / Q000187:drug effects* / Q000254:growth & development / Q000648:ultrastructure; D014031:Tobramycin / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D001425:Bacterial Outer Membrane Proteins; D005839:Gentamicins; D008055:Lipids; D010715:Phosphatidylglycerols; D000583:Amikacin; D014031:Tobramycin