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Adaptive resistance to aminoglycoside antibiotics in Pseudomonas aeruginosa
L B Gilleland1, H E Gilleland, J A Gibson
1Department of Microbiology and Immunology, Louisiana State University Medical Center, School of Medicine, Shreveport 71130.
Abstract:
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.
Insights
Pseudomonas aeruginosa developed resistance to aminoglycoside antibiotics like gentamicin. This resistance, linked to reduced drug uptake, was unstable and didn't affect other antibiotic types.
Area of Science:
- Microbiology
- Bacterial Genetics
- Drug Resistance Mechanisms
Background:
- Pseudomonas aeruginosa is an opportunistic pathogen known for developing antibiotic resistance.
- Aminoglycoside antibiotics are crucial for treating P. aeruginosa infections.
- Understanding resistance mechanisms is vital for effective antimicrobial strategies.
Purpose of the Study:
- To investigate the characteristics of aminoglycoside-resistant Pseudomonas aeruginosa variants.
- To explore the underlying mechanisms of adaptive resistance to gentamicin, tobramycin, and amikacin.
- To determine the stability and cross-resistance patterns of these resistant strains.
Main Methods:
- Selection of resistant strains by culturing P. aeruginosa in increasing aminoglycoside concentrations.
- Characterization of resistant strains for growth rate, stability, and cross-resistance.
- Assessment of cell envelope integrity and potential roles of protein H1 and phospholipids.
Main Results:
- Resistant P. aeruginosa strains were obtained, growing at 128-fold higher drug concentrations.
- Resistance was unstable without antibiotics and conferred cross-resistance to other aminoglycosides.
- Resistant strains showed altered permeability, with slower growth and minimal cell envelope damage.
- Protein H1 and phospholipid alterations were not significant factors in this resistance model.
- Resistance to aminoglycosides did not extend to polymyxin B.
Conclusions:
- Adaptive aminoglycoside resistance in P. aeruginosa is primarily linked to reduced permeability.
- This impermeability-based resistance is unstable and exhibits cross-resistance within the aminoglycoside class.
- The findings provide insights into P. aeruginosa's adaptive strategies against critical antibiotics.