Dysregulation of Cytosolic c-di-GMP in Edwardsiella piscicida Promotes Cellular Non-Canonical Ferroptosis

• DOI: 10.3389/fcimb.2022.825824
• Publication Date: 2022-02-04T12:03:44Z
• Authors: Ying Wen; Ying Wang; Shouwen Chen; Xiangshan Zhou; Yuanxing Zhang; Dahai Yang; Gabriel Núñez; Qin Liu
• Keywords: pathogen infection; 0303 health sciences; Virulence; bacterial virulence; Enterobacteriaceae Infections; Microbiology; non-canonical ferroptosis; QR1-502; 3. Good health; 03 medical and health sciences; c-di-GMP accumulation; Cellular and Infection Microbiology; Bacterial Proteins; Edwardsiella; Edwardsiella piscicida; Ferroptosis; Humans; Cyclic GMP; HeLa Cells

Programmed cell death plays an important role in modulating host immune defense and pathogen infection. Ferroptosis is a type of inflammatory induced by intracellular iron-dependent accumulation toxic lipid peroxides. Although ferroptosis has been associated with cancer other sterile diseases, very little known about the host-pathogen interactions. We show that secondary messenger bis-(3′,5′)-cyclic dimeric GMP (c-di-GMP) pathogenic bacterium Edwardsiella piscicida ( E. ) triggers non-canonical pathway infected HeLa cells. Moreover, we observed dysregulation c-di-GMP promotes iron accumulation, mitochondrial dysfunction, production reactive oxygen species, all which can be blocked chelator. Importantly, unlike classical executed via excess peroxidation, no peroxidation was detected Furthermore, lipoxygenases inhibitors lipophilic antioxidants are not able to suppress morphological changes mutant producing c-di-GMP, this attenuates bacterial virulence vivo . Collectively, our results reveal novel mediated provide evidence for regulation