Microbial quorum sensing and c-di-GMP–regulated biofilm pathways (QS/c-di-GMP pathways)

Microbial quorum sensing (QS) and cyclic diguanylate (c-di-GMP) signaling are interconnected regulatory networks that control bacterial behavior, particularly the transition from a planktonic (free-swimming) state to a biofilm-associated (sessile) state (Miller & Bassler, 2001; Römling et al., 2013). QS relies on the production and detection of chemical signal molecules called autoinducers to coordinate group behaviors such as virulence factor secretion and bioluminescence (Miller & Bassler, 2001). Concurrently, c-di-GMP acts as a ubiquitous bacterial second messenger where high intracellular levels generally promote biofilm formation and inhibit motility, while low levels favor dispersal (Römling et al., 2013). These pathways are critical in the pathogenesis of chronic infections, as biofilms provide a physical barrier against the host immune system and conventional antibiotics (Costerton et al., 1999). Targeting these systems, often referred to as anti-virulence or quorum-quenching strategies, aims to disarm pathogens without necessarily killing them, potentially reducing the selective pressure for antibiotic resistance (Hentzer et al., 2003). Drugs like azithromycin have been shown to inhibit QS at sub-inhibitory concentrations, while experimental compounds like baicalein and gallium nitrate target these pathways to disrupt biofilm integrity (Tateda et al., 2001; Luo et al., 2017; Kaneko et al., 2007). Overall, modulating these pathways represents a promising approach to treating persistent bacterial infections by enhancing the efficacy of existing antibiotics and the host immune response.

Other names

Bacterial quorum sensingc-di-GMP signalingQuorum quenching pathwaysBiofilm regulatory networksBacterial cell-to-cell communication

Inhibition of autoinducer synthesis, competitive antagonism of quorum sensing receptors (e.g., LuxR homologs), enzymatic degradation of autoinducers (quorum quenching), and modulation of c-di-GMP levels via inhibition of diguanylate cyclases (DGCs) or activation of phosphodiesterases (PDEs) (Hentzer et al., 2003; Römling et al., 2013).