Identification of a cellular role of hemolysin co-regulatory protein (Hcp) in Vibrio alginolyticus modulating substrate metabolism and biofilm formation by cAMP-CRP

Shuilong Wu; Yu Huang; Minhui Wu; Huapu Chen; Bei Wang; Kwaku Amoah; Jia Cai; Jichang Jian

doi:10.1016/j.ijbiomac.2024.136656

Identification of a cellular role of hemolysin co-regulatory protein (Hcp) in Vibrio alginolyticus modulating substrate metabolism and biofilm formation by cAMP-CRP

Int J Biol Macromol. 2024 Oct 16:136656. doi: 10.1016/j.ijbiomac.2024.136656. Online ahead of print.

Authors

Shuilong Wu¹, Yu Huang², Minhui Wu³, Huapu Chen², Bei Wang², Kwaku Amoah², Jia Cai⁴, Jichang Jian⁵

Affiliations

¹ Guangdong Provincial Key Laboratory of Aquatic Animal Disease Control and Healthy Culture, College of Fishery, Guangdong Ocean University, Zhanjiang 524088, China; Key Laboratory of Diseases Controlling for Aquatic Economic Animals of Guangdong Higher Education Institutions, College of Fishery, Guangdong Ocean University, Zhanjiang 524088, China; Central People's Hospital of Zhanjiang, Zhanjiang 524045, China.
² Guangdong Provincial Key Laboratory of Aquatic Animal Disease Control and Healthy Culture, College of Fishery, Guangdong Ocean University, Zhanjiang 524088, China; Key Laboratory of Diseases Controlling for Aquatic Economic Animals of Guangdong Higher Education Institutions, College of Fishery, Guangdong Ocean University, Zhanjiang 524088, China.
³ Central People's Hospital of Zhanjiang, Zhanjiang 524045, China.
⁴ Guangdong Provincial Key Laboratory of Aquatic Animal Disease Control and Healthy Culture, College of Fishery, Guangdong Ocean University, Zhanjiang 524088, China; Key Laboratory of Diseases Controlling for Aquatic Economic Animals of Guangdong Higher Education Institutions, College of Fishery, Guangdong Ocean University, Zhanjiang 524088, China. Electronic address: [email protected].
⁵ Guangdong Provincial Key Laboratory of Aquatic Animal Disease Control and Healthy Culture, College of Fishery, Guangdong Ocean University, Zhanjiang 524088, China; Key Laboratory of Diseases Controlling for Aquatic Economic Animals of Guangdong Higher Education Institutions, College of Fishery, Guangdong Ocean University, Zhanjiang 524088, China. Electronic address: [email protected].

PMID: 39423969
DOI: 10.1016/j.ijbiomac.2024.136656

Abstract

Cyclic AMP (cAMP) and cAMP receptor protein (CRP) system controls catabolic enzyme expression based on metabolite concentrations in bacteria. Hemolysin co-regulatory protein (Hcp) is well known as a molecular chaperone for virulence factor secretion of the type VI secretion system (T6SS). However, the intracellular role of Hcp involving in bacterial physiological processes remains unknown. To clarify that, we constructed a single hcp mutant strain and analyzed their effects on the physiological processes of Vibrio alginolyticus. The omics results revealed the extensive involvement of Hcp in the catabolic metabolism in bacteria. Simultaneously, Hcp1 and Hcp2 played opposing regulatory roles on the bacterial growth, biofilm formation, and intracellular cAMP-CRP levels during cultivation in a glucose medium. Furthermore, the interacting protein screening and co-immunoprecipitation (Co-IP) assays confirmed that the glucose-specific phosphoenolpyruvate (PEP)-phosphotransferase system (PTS) enzyme IIA component (EIIA^glc) was a key interacting partner with Hcp proteins as well as class I adenylyl cyclase (AC-I) in Vibrio alginolyticus. These results indicated that, to achieve cellular homeostasis, Hcp1 and Hcp2 might exert antagonistic and synergistic effects, respectively, on the interaction between EIIA^glc and AC thus cooperatively regulating intracellular cAMP-CRP production.

Keywords: Hcp; Metabolism; cAMP-CRP.