Fig 6. A proposed model of H2-T6SS-mediated Cu²⁺ transport in P. aeruginosa.

Under Cu²⁺ rich conditions, the copper homeostasis regulator CueR represses the expression of H2-T6SS genes. The Cu²⁺ transport is mainly dependent on the known systems, such as CopY, CueA and CusR/S. However, the repression of H2-T6SS by CueR is relieved under the Cu²⁺-limited conditions, and the Cu²⁺-binding protein Azu is subsequently secreted by the activated H2-T6SS. Secreted Azu scavenges extracellular Cu²⁺ and delivers its load via direct interaction with OprC.