Fig 7.

Proposed model of T4a pilin autoregulation by intramembrane interactions with the PilS sensor kinase. The PilR-PilS two-component system regulates major pilin biosynthesis in many T4aP-producing bacteria. Because PilS lacks a typical periplasmic sensor domain and controls the expression of pilins with diverse C-terminal sequences, it may instead detect the highly conserved N-terminal domain of PilA orthologs via intramembrane interactions (11). High intracellular levels of PilA, as in pilus assembly mutants, may inhibit pilA transcription in a manner that depends on sequences in the pilin's N terminus, possibly through modulation of PilS dimerization or stimulation of phosphatase activity of PilS on the response regulator, PilR (37, 338). When pilin levels are low—as in retraction-deficient mutants, where the pilins are trapped outside the cell—PilS kinase activity is stimulated, phosphorylating PilR and upregulating PilA transcription. The organization of the pilABCD genes in P. aeruginosa is shown. pilA is transcribed by σ⁵⁴, RNAP, and phospho-PilR from a divergent promoter that also controls expression of PilB (the pilin polymerase), PilC (the platform protein), and PilD (the prepilin peptidase).