Fig. 3

Mechanisms of T3SS and T6SS in regulating bacterial pathogenesis and host responses in P. aeruginosa. LPS is recognized by TLRs (TLR1/2 or TLR4/9) and then activates T3SS and T6SS.⁴⁷⁹ T3SS and and T6SS represent a critical network in regulating bacterial behaviors (growth, biofilm formation, and competition) and host defense (host cell apoptosis, inflammatory response, colonization, and motility). T6SS and T3SS interaction and inter-conversion are regulated by RtcB and YbeY. ExoS/ExoU induce P. aeruginosa-afflicted host cell apoptosis and colonization by targeting JNKS signal pathway. ExoY/ExoT reduces inflammasome activity through inhibition of bacterial motility to dampen NF-κB and caspase-1 activation. T6SS is a powerful antibacterial weapon that can be injected through multiple effectors to compete with other bacteria and allows P. aeruginosa colonization and biofilm formation^108,109