Suppression of Pseudomonas aeruginosa type III secretion system by a novel calcium-responsive signaling pathway

Jiahui Huang; Zirui Xu; Tian Zhou; Lian-Hui Zhang; Zeling Xu

doi:10.1016/j.isci.2024.109690

Suppression of Pseudomonas aeruginosa type III secretion system by a novel calcium-responsive signaling pathway

iScience. 2024 Apr 9;27(5):109690. doi: 10.1016/j.isci.2024.109690. eCollection 2024 May 17.

Authors

Jiahui Huang¹, Zirui Xu¹, Tian Zhou¹, Lian-Hui Zhang^{1

2}, Zeling Xu¹

Affiliations

¹ Guangdong Province Key Laboratory of Microbial Signals and Disease Control, Integrative Microbiology Research Centre, South China Agricultural University, Guangzhou, China.
² Guangdong Laboratory for Lingnan Modern Agriculture, South China Agricultural University, Guangzhou, China.

Abstract

Expression of the type III secretion system (T3SS) in Pseudomonas aeruginosa is exquisitely controlled by diverse environmental or host-related signals such as calcium (Ca²⁺), however, the signal transduction pathways remain largely elusive. In this study, we reported that FleR, the response regulator of the two-component system FleS/FleR, inhibits T3SS gene expression and virulence of P. aeruginosa uncoupled from its cognate histidine kinase FleS. Interestingly, FleR was found to repress T3SS gene expression under Ca²⁺-rich conditions independently of its DNA-binding domain. FleR activates the elevation of intracellular c-di-GMP contents and FleQ serves as the c-di-GMP effector to repress T3SS gene expression through the Gac/Rsm pathway. Remarkably, we found that AmrZ, a member of the FleR regulon, inhibits T3SS gene expression by directly targeting the promoter of exsCEBA in an expression level-dependent manner. This study revealed an intricate regulatory network that connects P. aeruginosa T3SS gene expression to the Ca²⁺ signal.

Keywords: Biochemistry; Microbial physiology; Microbiology.