Dual Regulatory Role Exerted by Cyclic Dimeric GMP To Control FsnR-Mediated Bacterial Swimming
Xin Zhang, Yan Wang, Yao Wu, Zhihui Yuan, Zhen Cai, Wei Qian, Xin Ge, Fangfang Wang
Abstract
Stenotrophomonas maltophilia has become a great threat to human health because of the high mortality of infected patients. Swimming motility plays a crucial role in regulating bacterial virulence and adaptation. However, limited progress has been made in cyclic dimeric GMP (c-di-GMP) controlling swimming motility of S. maltophilia. Here, we characterized c-di-GMP turnover enzymes encoded by S. maltophilia and dissected the regulatory details of a phosphodiesterase named SisP. We demonstrated that SisP degrades c-di-GMP to fully activate FsnR through directly releasing FsnR from the FsnR-c-di-GMP complex and indirectly increasing its phosphorylation level. This finding uncovered a quantitative, rather than an on-off, regulatory manner employed by c-di-GMP to regulate activities of its effectors. Identification of the specific activation of SisP by ferrous iron proposes SisP as a putative drug-target for controlling bacterial infection and ferrous iron at the wounds or cuts as a putative factor contributing to the higher risk of bacterial infection.