Antibiotic resistance in Pseudomonas aeruginosa is associated with decreased fitness.

The number of clinical specimens containing β-lactam-resistant Pseudomonas aeruginosa isolates is increasing. However, whether resistance is associated with reduced fitness is still uncertain in clinical Pseudomonas aeruginosa isolates. In this study, we aimed to determine whether β-lactam resistance conferred a fitness cost in Pseudomonas aeruginosa. Growth rate, extracellular slime production, elastase activity, proteolytic activity, LasA protease activity, biofilm formation, and pairwise in vitro competition experiments were investigated in a collection of 11 isogenic, β-lactam-susceptible and -resistant (≥8-fold increase in minimum inhibitory concentration (MIC)) pairs of P. aeruginosa clinical isolates; each pair was recovered from a different patient treated with β-lactam antibiotics. All β-lactam-resistant Pseudomonas aeruginosa isolates showed a significant reduction in elastase activity. In addition, 90.9% (10/11) of β-lactam-resistant Pseudomonas aeruginosa isolates were associated with markedly lower growth rate and proteolytic activity, and 81.8% (9/11) of β-lactam-resistant Pseudomonas aeruginosa isolates had less extracellular slime production, compared to susceptible isolates. Meanwhile, LasA protease activity and biofilm formation ability were variable among isolates. Pairwise in vitro competition experiments showed that 72.7% (8/11) of β- lactam-susceptible strains could outgrow resistant strains. In conclusion, resistance development with β-lactam exposure confers a fitness cost, resulting in a decreased invasion potential, while the effect on viability varied. Thus, the potential for the dissemination of β-lactam-resistant Pseudomonas aeruginosa clinical isolates should not be underestimated.