title: Vitamin K3Induces the Expression of the Stenotrophomonas maltophilia SmeVWX Multidrug Efflux Pump.
abstract: Stenotrophomonas maltophiliais an opportunistic pathogen with increasing prevalence, which is able to cause infections in immunocompromised patients or in those with a previous pathology. The treatment of the infections caused by this bacterium is often complicated due to the several intrinsic antibiotic resistance mechanisms that it presents. Multidrug efflux pumps are among the best-studied mechanisms ofS. maltophiliaantibiotic resistance. Some of these efflux pumps have a basal expression level but, in general, their expression is often low and only reaches high levels when the local regulator is mutated or bacteria are in the presence of an effector. In the current work, we have developed a yellow fluorescent protein (YFP)-based sensor with the aim to identify effectors able to trigger the expression of SmeVWX, an efflux pump that confers resistance to quinolones, chloramphenicol, and tetracycline when it is expressed at high levels. With this purpose in mind, we tested a variety of different compounds and analyzed the fluorescence signal given by the expression of YFP under the control of thesmeVWXpromoter. Among the tested compounds, vitamin K3, which is a compound belonging to the 2-methyl-1,4-naphthoquinone family, is produced by plants in defense against infection, and has increasing importance in human therapy, was able to induce the expression of the SmeVWX efflux pump. In addition, a decrease in the susceptibility ofS. maltophiliato ofloxacin and chloramphenicol was observed in the presence of vitamin K3, in both wild-type andsmeW-deficient strains.
authors.affiliation: Centro Nacional de Biotecnología, CSIC, Madrid, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Blanco
authors.affiliation: Centro Nacional de Biotecnología, CSIC, Madrid, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Corona
authors.affiliation: Centro Nacional de Biotecnología, CSIC, Madrid, Spain.
authors.forename: M B
authors.initials: MB
authors.lastname: Sánchez
authors.affiliation: Centro Nacional de Biotecnología, CSIC, Madrid, Spain jlmtnez@cnb.csic.es.
authors.forename: J L
authors.initials: JL
authors.lastname: Martínez
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins; D001693:Biological Transport, Active / Q000502:physiology*; D015374:Biosensing Techniques; D002701:Chloramphenicol / Q000494:pharmacology; D024901:Drug Resistance, Multiple, Bacterial / Q000502:physiology*; D006801:Humans; D008164:Luminescent Proteins; D026901:Membrane Transport Proteins / Q000096:biosynthesis*; D008826:Microbial Sensitivity Tests; D015242:Ofloxacin / Q000494:pharmacology; D015363:Quinolones / Q000494:pharmacology; D020615:Stenotrophomonas maltophilia / Q000187:drug effects / Q000378:metabolism*; D013752:Tetracycline / Q000494:pharmacology; D024483:Vitamin K 3 / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D008164:Luminescent Proteins; D026901:Membrane Transport Proteins; D015363:Quinolones; C054562:yellow fluorescent protein, Bacteria; D002701:Chloramphenicol; D024483:Vitamin K 3; D015242:Ofloxacin; D013752:Tetracycline
keywords: SmeVWX; Stenotrophomonas maltophilia; biosensors; efflux pumps; inducible resistance