Work

Mutation of smeRv Renders Stenotrophomonas maltophilia Resistant to First-Line Antibiotics Trimethoprim/Sulfamethoxazole and Levofloxacin

Year: 2025

Type: article

Abstract: Background: Stenotrophomonas maltophilia is one of the common causative agents of hospital-acquired infections worldwide. The major concern regarding S. maltophilia infections is its extreme resistance to multiple antibiotics. Methods: Enrofloxacin-resistant mutants of S. maltophilia K279a were selected using a serial passage technique. Results: In this study, we showed that one of the mutant strains, KE507, which was selected from S. maltophilia K279a for its resistance to the veterinary drug enrofloxacin, conferred resistance to trimethoprim/sulfamethoxazole (co-trimoxazole), levofloxacin, and minocycline as per the Clinical and Laboratory Standards Institute guideline. These antibiotics are the first-line drugs routinely used to treat S. maltophilia infections. The KE507 mutant also showed increased resistance to all tested quinolones, azithromycin, and neomycin. Molecular characterization using whole genome sequencing, antibiotic resistance gene expression profiles, and mutational analysis indicated that inactivation of SmeRv (Q208insHSPRFTW), a transcriptional regulator of the SmeVWX multidrug efflux pump, contributes to resistance to quinolones (including levofloxacin), co-trimoxazole, and partially to neomycin, but not to azithromycin or minocycline. These data, together with in silico structural analysis, suggest that the mutation of SmeRv causes a conformational change in the SmeRv structure, which leads to the activation of SmeVWX efflux transporter expression and subsequent resistance to co-trimoxazole and quinolone antibiotics. Conclusion:S. maltophilia can thus acquire resistance to the antibiotics primarily used to treat S. maltophilia infections through the mutation of SmeRv.

Source: Antibiotics

DOI: 10.3390/antibiotics14060550

Authors: Nuchjaree Boonyong, Nisanart Charoenlap, Parinya Tipanyo, Pitthawat Grittanaanun, Skorn Mongkolsuk, Paiboon Vattanaviboon

Institutions: Chulabhorn Graduate Institute, Chulabhorn Research Institute, Ministry of Higher Education, Science, Research and Innovation

Language: English

Topic: Infections and bacterial resistance

Subfield: Endocrinology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,499