Model of NspS-MbaA signalling pathway. (a) When NspS is bound by norspermidine, the PDE activity of MbaA is inhibited, leading to accumulation of c-di-GMP and increased biofilm formation. (b) Intermediate state of interaction in which NspS interacts with the periplasmic domain of MbaA to inhibit the PDE activity of MbaA, leading to intermediate levels of c-di-GMP and biofilm formation. (c) When NspS is bound by spermine (or spermidine), the inhibition of the PDE activity of MbaA is relieved, resulting in enhanced c-di-GMP degradation and low biofilm formation. Black triangles represent c-di-GMP and black circles represent 5’pGpG. Nspd and spm stand for norspermidine and spermine, respectively. The structure of norspermidine is shown in green and the structure of spermine is in blue. OM stands for outer membrane and IM for inner membrane.