SmQnrR, a DeoR-type transcriptional regulator, negatively regulates the expression of Smqnr and SmtcrA in Stenotrophomonas maltophilia

Objectives: To characterize the role of SmqnrR in the expression of Smqnr and SmtcrA, and the role of SmtcrA in drug resistance in Stenotrophomonas maltophilia. Methods: SmqnrR, a DeoR-type regulator gene, is situated between a quinolone resistance gene (Smqnr) and a putative major facilitator superfamily transmembrane transporter gene (SmtcrA). To assess the regulatory role of SmQnrR in the expression of Smqnr and SmtcrA, the transcripts of Smqnr and SmtcrA genes were determined in the wild-type KJ and the SmqnrR isogenic mutant KJΔQnrR. An SmqnrR polar mutant, KJΔQnrRV, was constructed to investigate the possibility that SmqnrR and SmtcrA form an operon. The contribution of Smqnr and SmtcrA genes to the intrinsic and acquired resistance of S. maltophilia was evaluated using susceptibility testing. Results: SmQnrR acted as a repressor for the expression of Smqnr and SmtcrA genes. SmqnrR and SmtcrA genes formed an operon, which was negatively autoregulated by SmQnrR. Smqnr and SmtcrA contributed only slightly to intrinsic resistance in S. maltophilia. Nevertheless, overexpression of Smqnr and SmtcrA by inactivating SmqnrR conferred a slight increase in quinolone MICs and a more marked increase in tetracycline MIC. Conclusions: The SmQnrR protein is a transcriptional repressor for the contiguous Smqnr and SmtcrA genes, and SmQnrR is a negative regulator of SmqnrR-SmtcrA operon expression. Inactivation of SmqnrR contributes to an acquired increase in quinolone and tetracycline MICs for S. maltophilia.