The SmeYZ efflux pump of Stenotrophomonas maltophilia contributes to drug resistance, virulence-related characteristics, and virulence in mice.
The resistance-nodulation-division (RND)-type efflux pump is one of the causes of the multidrug resistance of Stenotrophomonas maltophilia. The roles of the RND-type efflux pump in physiological functions and virulence, in addition to antibiotic extrusion, have attracted much attention. In this study, the contributions of the constitutively expressed SmeYZ efflux pump to drug resistance, virulence-related characteristics, and virulence were evaluated. S. maltophilia KJ is a clinical isolate of multidrug resistance. The smeYZ isogenic deletion mutant, KJΔYZ, was constructed by a gene replacement strategy. The antimicrobial susceptibility, virulence-related physiological characteristics, susceptibility to human serum and neutrophils, and in vivo virulence between KJ and KJΔYZ were comparatively assessed. The SmeYZ efflux pump contributed resistance to aminoglycosides and trimethoprim-sulfamethoxazole. Inactivation of smeYZ resulted in attenuation of oxidative stress susceptibility, swimming, flagella formation, biofilm formation, and secreted protease activity. Furthermore, loss of SmeYZ increased susceptibility to human serum and neutrophils and decreased in vivo virulence in a murine model. These findings suggest the possibility of attenuation of the resistance and virulence of S. maltophilia with inhibitors of the SmeYZ efflux pump.
Division of Infectious Diseases, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan School of Medicine, National Yang-Ming University, Taipei, Taiwan.
Yi-Tsung
YT
Lin
Department of Biotechnology and Laboratory Science in Medicine, National Yang-Ming University, Taipei, Taiwan.
Yi-Wei
YW
Huang
Department of Life Science, Institute of Ecology and Evolutionary Biology and TechComm-5, College of Life Science, National Taiwan University, Taipei, Taiwan.
Shiang-Jiuun
SJ
Chen
Department of Biotechnology and Laboratory Science in Medicine, National Yang-Ming University, Taipei, Taiwan.
Chia-Wei
CW
Chang
Department of Biotechnology and Laboratory Science in Medicine, National Yang-Ming University, Taipei, Taiwan tcyang@ym.edu.tw.
Tsuey-Ching
TC
Yang
D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism*; D018441:Biofilms; D004202:Disinfectants / Q000494:pharmacology; D024881:Drug Resistance, Bacterial / Q000235:genetics; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics; D005407:Flagella / Q000235:genetics; D017353:Gene Deletion; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008826:Microbial Sensitivity Tests; D009154:Mutation / Q000235:genetics; D009504:Neutrophils / Q000276:immunology; D010447:Peptide Hydrolases / Q000737:chemistry / Q000378:metabolism; D020615:Stenotrophomonas maltophilia / Q000235:genetics* / Q000472:pathogenicity*; D014774:Virulence / Q000235:genetics; D037521:Virulence Factors / Q000235:genetics* / Q000378:metabolism*; D024483:Vitamin K 3 / Q000494:pharmacology
D001426:Bacterial Proteins; D004202:Disinfectants; D026901:Membrane Transport Proteins; D037521:Virulence Factors; D024483:Vitamin K 3; D006861:Hydrogen Peroxide; D010447:Peptide Hydrolases