FIG 7.

A model illustrating the regulation of H1-T6SS expression by FleS/FleR in PAO1. H1-T6SS is poorly expressed in PAO1 WT under laboratory conditions, which is mainly achieved by the RetS/Gac/Rsm pathway. The RetS/Gac/Rsm pathway regulates H1-T6SS at post-transcriptional level by release or sequester the central factor RsmA. In this study, we revealed a novel pathway under the control of the two-component system FleS/FleR which is independent of the RetS/Gac/Rsm pathway. FleS/FleR activates AmrZ to induce the synthesis of intracellular c-di-GMP, which subsequently represses the expression and activity of the H1-T6SS through FleQ. In the ΔfleR mutant, reduced c-di-GMP content leads to the de-repression and activation of H1-T6SS regardless of the presence of RetS and RsmA with unknown mechanisms.