Evolution of Resistance against Ciprofloxacin, Tobramycin, and Trimethoprim/Sulfamethoxazole in the Environmental Opportunistic Pathogen Stenotrophomonas maltophilia

is an opportunistic pathogen that produces respiratory infections in immunosuppressed and cystic fibrosis patients. The therapeutic options to treat infections are limited since it exhibits resistance to a wide variety of antibiotics such as β-lactams, aminoglycosides, tetracyclines, cephalosporins, macrolides, fluoroquinolones, or carbapenems. The antibiotic combination trimethoprim/sulfamethoxazole (SXT) is the treatment of choice to combat infections caused by , while ceftazidime, ciprofloxacin, or tobramycin are used in most SXT-resistant infections. In the current study, experimental evolution and whole-genome sequencing (WGS) were used to examine the evolutionary trajectories of towards resistance against tobramycin, ciprofloxacin, and SXT. The genetic changes underlying antibiotic resistance, as well as the evolutionary trajectories toward that resistance, were determined. Our results determine that genomic changes in the efflux pump regulatory genes and are essential to confer resistance to ciprofloxacin, and the mutation in the gene is significant in the resistance to tobramycin. We identified mutations in and the efflux pump regulator as the basis of SXT resistance. Detailed and reliable knowledge of ciprofloxacin, tobramycin, and SXT resistance is essential for safe and effective use in clinical settings. Herein, we were able to prove once again the extraordinary ability that has to acquire resistance and the importance of looking for alternatives to combat this resistance.