Two-Component Signal Transduction Systems: A Major Strategy for Connecting Input Stimuli to Biofilm Formation

Abstract

Biofilms are multicellular communities of microbes that are encased within an extracellular matrix. Environmental factors induce bacteria to form biofilm. Bacteria have several regulatory mechanisms in response to environmental changes, and the two-component signal transduction system (TCS) is a major strategy in connecting changes in input signals to changes in cellular physiological output. The TCS employs multiple mechanisms such as cross-regulation, to integrate and coordinate various input stimuli to control biofilm formation. In this mini-review, we demonstrate the roles of TCS on biofilm formation, illustrating these input signals and modulation modes, which may be utilized by future investigations in elucidating the regulatory signals and underlying the mechanisms of biofilm formation.

Keywords: biofilm; c-di-GMP; cross-regulation; input signals; two-/three-/multi-component signal transduction systems.

Figure 1

Two-/three-/multi-component signal transduction system modulation patterns. (A) (i) The classical version comprises an N-terminal input domain (purple), followed by a transmitter (H1) domain (red) with a conserved histidine that can be autophosphorylated in histidine kinase (HK). The phosphoryl group (P) can be transferred to a conserved aspartic residue in the receiver (D1) domain (blue) in the response regulator (RR). The classical version is a two-step phosphorelay mechanism; (ii) in the unorthodox version, the H1 domain is followed by an additional conserved aspartic residue (D1) and an H2 (yellow) domain in the C-terminal of HK. The phosphoryl group (P) can be transferred to a conserved aspartic residue in the receiver (D2) domain (green) in the RR. The unorthodox version is a four-step phosphorelay mechanism. (iii) the hybrid version is similar to the unorthodox version. The only difference is that the H2 (Hpt) domain of the hybrid version is an external phosphotransfer module that acts as an individual protein. (B) The modulation mode of the Hno-multi-component signal transduction system. (C) The modulation mode of the Lrb-three-component signal transduction system. (D) The modulation mode of the Gac-multi-component signaling transduction system; the red arrow indicates that the phosphoryl group (P) can be transferred from the D1 domain of LadS to the H2 domain of GacS. Arrows indicate activation, and the flat end represents inhibition. Solid arrows indicate direct regulation, and dashed arrows represent indirect regulation. Inner membrane (IM), periplasm (P), cytoplasm (C).

Figure 2

Cross-regulation patterns and the “control system” with TCS. (A) Cross-regulation between PmrB-PmrA and QseC-QseB. (i) The regulatory pattern in QseC-activated conditions; (ii) The regulatory pattern in PmrB-activated conditions. (B) Solid surface signal activates TCS ChpA-PilG by TFP. Thick arrows indicate robust regulation, and thin arrows represent weak regulation. Inner membrane (IM). Periplasm (P), cytoplasm (C).