Tetracycline-modifying enzymeSmTetX fromStenotrophomonas maltophilia

Abstract

The resistance of the emerging human pathogenStenotrophomonas maltophiliato tetracycline antibiotics mainly depends on multidrug efflux pumps and ribosomal protection enzymes. However, the genomes of several strains of this Gram-negative bacterium code for a FAD-dependent monooxygenase (SmTetX) homologous to tetracycline destructases. This protein was recombinantly produced and its structure and function were investigated. Activity assays usingSmTetX showed its ability to modify oxytetracycline with a catalytic rate comparable to those of other destructases.SmTetX shares its fold with the tetracycline destructase TetX fromBacteroides thetaiotaomicron; however, its active site possesses an aromatic region that is unique in this enzyme family. A docking study confirmed tetracycline and its analogues to be the preferred binders amongst various classes of antibiotics.