The SmeYZ Efflux Pump of Stenotrophomonas maltophilia Contributes to Drug Resistance, Virulence-Related Characteristics, and Virulence in Mice

Abstract

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, KJ⌬YZ, 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 KJ⌬YZ 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.

Genotypic and Phenotypic Characterization of Stenotrophomonas maltophilia Strains from a Pediatric Tertiary Care Hospital in Serbia

“…Different factors influenc biofilm formation in S . maltophilia , namely SmeYZ efflux pump that also confers resistance to antimicrobials [33], iron level in the media [34], and histidin kinase and BfmAK system [35]. Apart from biofilm formation, other physiological functions (such as swimming moility, oxidative stres regulation, etc.)…”

Vitamin K 3 Induces the Expression of the Stenotrophomonas maltophilia SmeVWX Multidrug Efflux Pump

“…Expression of these determinants is usually repressed by specific regulators encoded by genes located upstream of the operons that contain the structural genes for these efflux pumps (19). In the opportunistic pathogen S. maltophilia, some of these RND multidrug efflux pumps, such as SmeDEF, SmeIJK, SmeOP, and SmeYZ, contribute to bacterial intrinsic resistance (4,6,9,14), while others, such as SmeVWX, have very low levels of expression and its overexpression alone leads to acquired resistance (11,22). In addition to genetic alterations, resistance can also be achieved by the presence of effectors or conditions that trigger the expression of multidrug efflux pumps, leading to the acquisition of transient phenotypic antibiotic resistance (25)(26)(27).…”

“…The roles of six of them (SmeABC, SmeDEF, SmeIJK, SmeOP, SmeVWX, and SmeYZ) in intrinsic and acquired resistance to antibiotics have been analyzed (5)(6)(7)(8)(9)(10)(11)(12)(13)(14).…”

Overexpression of SmeDEF Efflux Pump Decreases Aminoglycoside Resistance in Stenotrophomonas maltophilia

“…The resistance to AGs reported in S. maltophilia is attributable to aminoglycoside-modifying enzymes (AMEs), RND-type efflux pumps, and outer membrane permeability (8,13,(14)(15)(16). Given that SmeT acts as a transcriptional repressor, we wondered whether SmeT also regulates the expression of AMEs, RND-type efflux pumps, and lytic transglycosidase genes, in addition to the smeDEF operon.…”