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Emergence of multidrug-resistant mutants is increased under antibiotic selective pressure in Pseudomonas aeruginosa
A Alonso1, E Campanario, J L Martínez
1Departamento de Biotecnología Microbiana, Centro Nacional de Biotecnología (CSIC), Cantoblanco, Madrid, Spain.
Abstract:
Pseudomonas aeruginosa is one of the most important opportunistic pathogens involved in nosocomial infections, cystic fibrosis patients included. Hospital isolates frequently present multidrug-resistance (MDR) phenotypes as the consequence of constant antibiotic selective pressure. The kinetics of emergence of P. aeruginosa MDR mutants under antibiotic selective pressure indicated that long-term incubation in the presence of the bacteriostatic antibiotic tetracycline increases the mutation rate per cell per day of P. aeruginosa PAO1 by several orders of magnitude. The tetracycline-resistant mutants obtained were stable, showed decreased susceptibility to antibiotics belonging to different structural families, and contained an outer-membrane protein not present in the wild-type P. aeruginosa strain PAO1. These data are consistent with the hypothesis that incubation in the presence of tetracycline favours the emergence of MDR mutants in P. aeruginosa. The results are relevant for understanding the rapid emergence of antibiotic-resistant mutants among bacterial populations during infections. Their relationship to other models of increased mutagenesis under stress is discussed with respect to the adaptive mutation phenomenon.
Insights
Long-term exposure to tetracycline significantly increases the mutation rate of Pseudomonas aeruginosa, promoting the emergence of multidrug-resistant (MDR) strains. These resistant mutants exhibit reduced susceptibility to various antibiotics.
Area of Science:
- Microbiology
- Molecular Biology
- Infectious Diseases
Background:
- Pseudomonas aeruginosa is a critical opportunistic pathogen causing hospital-acquired infections, particularly in cystic fibrosis patients.
- Multidrug-resistance (MDR) is a common phenotype in hospital isolates due to antibiotic selective pressure.
Purpose of the Study:
- To investigate the effect of the bacteriostatic antibiotic tetracycline on the mutation rate of Pseudomonas aeruginosa.
- To characterize the resulting MDR mutants and understand the mechanism of resistance emergence.
Main Methods:
- Incubation of Pseudomonas aeruginosa PAO1 with tetracycline over an extended period.
- Analysis of mutation rates, antibiotic susceptibility, and outer-membrane protein profiles of resulting mutants.
Main Results:
- Tetracycline treatment increased the mutation rate of P. aeruginosa by several orders of magnitude.
- Obtained tetracycline-resistant mutants were stable and displayed cross-resistance to other antibiotic classes.
- These mutants possessed a novel outer-membrane protein absent in the wild-type strain.
Conclusions:
- Incubation with tetracycline promotes the emergence of MDR mutants in Pseudomonas aeruginosa.
- Findings offer insights into the rapid development of antibiotic resistance in bacterial populations during infections.
- The study supports the adaptive mutation phenomenon under stress conditions.