2. Academic Validation
  3. Multilevel regulation of c-di-GMP biosynthesis by cAMP signaling increases Shigella sonnei fitness and pathogenicity in response to bile salts

Multilevel regulation of c-di-GMP biosynthesis by cAMP signaling increases Shigella sonnei fitness and pathogenicity in response to bile salts

  • Cell Rep. 2025 Sep 17;44(10):116306. doi: 10.1016/j.celrep.2025.116306.
Mingfang Wang 1,  Jia Zeng 2,  Binbin Cui 3,  Guangliang Wu 4,  Xiayu Chen 2,  Yikai Fu 2,  Bing Gu 5,  Yinyue Deng 6
Affiliations

Affiliations

  • 1 Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Science, Guangzhou 510000, China; Laboratory Medicine, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong 510080, China; School of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Sun Yat-sen University, Shenzhen 518107, China.
  • 2 School of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Sun Yat-sen University, Shenzhen 518107, China.
  • 3 Pharmacy Department, The Affiliated LiHuiLi Hospital of Ningbo University, Ningbo 315046, China.
  • 4 Pharmacy Department, Ningbo No. 2 Hospital, Ningbo 315010, China.
  • 5 Laboratory Medicine, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong 510080, China. Electronic address: gubing@gdph.org.cn.
  • 6 School of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Sun Yat-sen University, Shenzhen 518107, China. Electronic address: dengyle@mail.sysu.edu.cn.
PMID: 40966079 DOI: 10.1016/j.celrep.2025.116306
Abstract

It was previously demonstrated that intestinal pathogens have evolved different mechanisms to enhance their Infection and colonization in the intestines of hosts. However, it is unclear how Shigella effectively survives in the presence of bile salts. Here, we report that the biofilm formation and pathogenicity of S. sonnei are induced by primary bile salts through the two-component system EvgS/EvgA. The response regulator EvgA controls the transcription of the cyclic AMP synthase-encoding gene. Furthermore, the effector protein CRP of the cyclic AMP (cAMP) signal not only positively controls the transcription of ydeH, a gene encoding cyclic di-GMP (c-di-GMP) synthase, but also forms a complex with YdeH to improve its catalytic production of c-di-GMP. Additionally, interacting with YdeH enhances the ability of CRP to bind to the promoter of ydeH. Our work provides insights into how S. sonnei utilizes cascade amplification of c-di-GMP to promote fitness and pathogenicity in response to primary bile salts.

Keywords

CP: Microbiology; Shigella sonnei; bile salts; c-di-GMP; cAMP; pathogenicity.

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