Induction of Antimicrobial Resistance of Stenotrophomonas maltophilia by Exposure to Nonlethal Levels of Antibiotics

Abstract

The effects of the sequential subculture in the presence of a driving force on antimicrobial resistance of Stenotrophomonas maltophilia K279a were investigated. Stationary-phase cells were inoculated into the lysogeny broth medium, with and without antibiotic supplementation, and grown until the stationary phase before being subcultured into the same antibiotic-supplemented medium for six consecutive cycles. Thirty colonies from each cycle and treatment condition were selected and their antibiotic susceptibility profiles were determined. The sequential subculture of K279a for a number of cycles reduced susceptibility to diverse classes of antibiotics, including ciprofloxacin, amikacin, gentamicin, ceftazidime, co-trimoxazole, and chloramphenicol, regardless of the antibiotic used. Supplementation with antibiotics that is, ampicillin, kanamycin, ciprofloxacin, and ceftazidime, at sublethal concentrations significantly accelerated the development rate of strains that reduced susceptibility to other antibiotics. The patterns of reduced susceptibility were different depending on the antibiotic used for supplementation. Thus, without gene transfer, antibiotic-resistant strains of S. maltophilia can readily develop, especially after antibiotic treatments. Whole-genome sequence analysis of the selected antibiotic-resistant mutants identified gene mutations that might be responsible for antimicrobial resistance of S. maltophilia.