Role of the two-component system CiaRH in the regulation of efflux pump SatAB and its correlation with fluoroquinolones susceptibility

Streptococcus suis is a zoonotic pathogen with a high incidence and mortality rate in both swine and humans. Following antibiotic treatment, the organism has evolved many resistance mechanisms, among of which efflux pump overexpression can promote drug extrusion out of the cell. This study clarified the role of CiaRH in fluoroquinolone resistance. A deletion of the ciaRH genes showed decreased susceptibility to tested antibiotics, an invariant growth rate, and reduced intracellular substrates. This research also demonstrated that the overexpression of efflux pump, SatAB, was the main cause of ∆ciaRH resistance. In addition, CiaR could combine with the promoter region of satAB, to further directly suppress target gene transcription. Simultaneously, satAB was also directly regulated by SatR. Our findings may provide novel insight into the development of drug targets, and help exploit corresponding inhibitors to combat bacterial multidrug resistance.