Vitamin K3 Induces the Expression of the Stenotrophomonas maltophilia SmeVWX Multidrug Efflux Pump

Antimicrob Agents Chemother. 2017 Apr 24;61(5):e02453-16. doi: 10.1128/AAC.02453-16. Print 2017 May.

Abstract

Stenotrophomonas maltophilia is 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 of S. maltophilia antibiotic 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 the smeVWX promoter. 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 of S. maltophilia to ofloxacin and chloramphenicol was observed in the presence of vitamin K3, in both wild-type and smeW-deficient strains.

Keywords: SmeVWX; Stenotrophomonas maltophilia; biosensors; efflux pumps; inducible resistance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Bacterial Proteins
  • Biological Transport, Active / physiology*
  • Biosensing Techniques
  • Chloramphenicol / pharmacology
  • Drug Resistance, Multiple, Bacterial / physiology*
  • Humans
  • Luminescent Proteins
  • Membrane Transport Proteins / biosynthesis*
  • Microbial Sensitivity Tests
  • Ofloxacin / pharmacology
  • Quinolones / pharmacology
  • Stenotrophomonas maltophilia / drug effects
  • Stenotrophomonas maltophilia / metabolism*
  • Tetracycline / pharmacology
  • Vitamin K 3 / metabolism*

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Luminescent Proteins
  • Membrane Transport Proteins
  • Quinolones
  • yellow fluorescent protein, Bacteria
  • Chloramphenicol
  • Vitamin K 3
  • Ofloxacin
  • Tetracycline