Fig. 2.

Contribution of SagS to the motile-sessile and susceptible-resistance switch in P. aeruginosa. Transition to the irreversible attachment stage, in which SagS directly interacts with and phosphorylates the TCS BfiSR [60,61], marks the timing when surface-associated cells start to be resistant to antimicrobial agents [68]. SagS regulates the switch from an antimicrobial susceptible to a highly tolerant state via regulation of c-di-GMP levels [88], which are generated by the diguanylate cyclase PA3177 [67], and subsequent activation of BrlR in a phosphotransfer-independent manner [67,68,95]. BrlR, in turn, modulates the expression of multidrug efflux pumps and ABC transporter [12,22]. Gray arrows with dashed lines indicate unidentified mechanism(s).