Appl Environ Microbiol. 2014; pii: AEM.01058-14.

García-León G, Hernández A, Hernando-Amado S, Alavi P, Berg G, Martínez JL.

Quinolones are synthetic antibiotics and the main cause of resistance to these antimicrobials is mutation of the genes encoding their targets. However, differing to other organisms, such mutations have not been found in quinolone resistant Stenotrophomonas maltophilia isolates, in which overproduction of the SmeDEF efflux pump is a major cause of quinolone resistance.

SmeDEF is chromosomally encoded and highly conserved in all studied S. maltophilia strains; it is an ancient element that evolved over millions of years in this species. It seems then difficult that its main function would be resistance to quinolones, a family of synthetic antibiotics not present in natural environments until the last decades. Expression of SmeDEF is tightly controlled by the transcriptional repressor SmeT.

Our work shows that plant-produced flavonoids can bind SmeT releasing it from smeDEF and smeT operators. Antibiotics extruded by SmeDEF do not impede the binding of SmeT to DNA. The fact that plant-produced flavonoids specifically induce smeDEF expression indicate they are bona fide effectors regulating expression of this resistance determinant. Expression of efflux pumps is usually down-regulated, unless their activity is needed. Since smeDEF expression is triggered by plant-produced flavonoids, we reasoned this efflux pump may have a role in the colonization of plants by S. maltophilia. Our results showed that, indeed, deletion of smeE impairs S. maltophilia colonization of plant roots.

Altogether, our results indicate that quinolone resistance is a recent function of SmeDEF and the colonization of plant roots is likely one original function of this efflux pump.