Yao Junmin, Li Shaohuihao, Wu Xuefan, Qin Shuangkang, Lei Chengfeng, Sun Xiulian, Hu Jia
Center for Biosafety Mega-Science, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, China.
University of Chinese Academy of Sciences, Beijing, China.
World J Microbiol Biotechnol. 2025 Apr 28;41(5):143. doi: 10.1007/s11274-025-04353-3.
Bacillus anthracis is the causative agent of anthrax disease. Our prior research indicated that cyclic (c)-di-AMP accumulation attenuated bacterial virulence in mice. However, the function of c-di-AMP secretion and its regulatory mechanism in anthrax have not been revealed. We characterized the role of the ecto-nucleotidase CpdB in B. anthracis. CpdB exhibits phosphodiesterase activity towards c-di-AMP and 2'3'-cGMP-AMP, and nucleotidase activity towards several mononucleotides, including the preferred substrates c-di-AMP and pApA. Our results demonstrated that inactivation of cpdB altered purine nucleotide metabolism, decreasing the levels of anthrax toxins and extracellular proteases while increasing the expression of adhesion factor BslA. The rates of adhesion and invasion of B. anthracis to both endothelial cells and immune cells in vitro were enhanced by cpdB inactivation. In infected silkworms, cpdB inactivation led to higher levels of colonization in hemolymph, but virulence was attenuated. These findings suggest that cpdB has pleiotropic functions in the infection and virulence of B. anthracis.
炭疽芽孢杆菌是炭疽病的病原体。我们之前的研究表明，环二腺苷酸（c-di-AMP）的积累会减弱细菌在小鼠体内的毒力。然而，炭疽中c-di-AMP分泌的功能及其调控机制尚未被揭示。我们对炭疽芽孢杆菌中外切核苷酸酶CpdB的作用进行了表征。CpdB对c-di-AMP和2'3'-环鸟苷酸腺苷（2'3'-cGMP-AMP）表现出磷酸二酯酶活性，对几种单核苷酸表现出核苷酸酶活性，包括优选底物c-di-AMP和对氨基苯磷酸（pApA）。我们的结果表明，cpdB的失活改变了嘌呤核苷酸代谢，降低了炭疽毒素和细胞外蛋白酶的水平，同时增加了粘附因子BslA的表达。cpdB失活增强了炭疽芽孢杆菌在体外对内皮细胞和免疫细胞的粘附和侵袭率。在感染的家蚕中，cpdB失活导致血淋巴中的定殖水平更高，但毒力减弱。这些发现表明，cpdB在炭疽芽孢杆菌的感染和毒力中具有多效性功能。
