Chemoproteomic profiling of host and pathogen enzymes active in cholera.
Chemoproteomic profiling of host and pathogen enzymes active in cholera.
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DOI：
10.1038/nchembio.2025
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发表时间：
2016-04
影响因子：
14.8
通讯作者：
Waldor MK
中科院分区：
文献类型：
--
作者：
Hatzios SK;Abel S;Martell J;Hubbard T;Sasabe J;Munera D;Clark L;Bachovchin DA;Qadri F;Ryan ET;Davis BM;Weerapana E;Waldor MK
基于活性的蛋白质谱（ABPP）是一种检测复杂生物系统中活性酶的化学蛋白质组学工具。我们使用ABPP来鉴定分泌的细菌和宿主丝氨酸水解酶，这些丝氨酸水解酶在感染霍乱病原体霍乱弧菌的动物中是活跃的。四种霍乱弧菌蛋白酶在感染的兔子中始终具有活性，其中一种，VC 0157（重命名为IvaP），在人霍乱粪便中也具有活性。IvaP的失活影响了体内其他分泌的霍乱弧菌和兔酶的活性，而所有四种蛋白酶的遗传破坏增加了感染兔中肠凝集素- Intelectin也结合到其他肠道细菌病原体，这表明它可能构成了一个以前未被认识到的机制，细菌监视肠道中的病原体分泌的蛋白酶抑制。我们的工作证明了基于活性的蛋白质组学在动物感染模型中揭示宿主-病原体酶对话的能力。
Activity-based protein profiling (ABPP) is a chemoproteomic tool for detecting active enzymes in complex biological systems. We used ABPP to identify secreted bacterial and host serine hydrolases that are active in animals infected with the cholera pathogen Vibrio cholerae. Four V. cholerae proteases were consistently active in infected rabbits, and one, VC0157 (renamed IvaP), was also active in human cholera stool. Inactivation of IvaP influenced the activity of other secreted V. cholerae and rabbit enzymes in vivo, while genetic disruption of all four proteases increased the abundance and binding of an intestinal lectin—intelectin—to V. cholerae in infected rabbits. Intelectin also bound to other enteric bacterial pathogens, suggesting it may constitute a previously unrecognized mechanism of bacterial surveillance in the intestine that is inhibited by pathogen-secreted proteases. Our work demonstrates the power of activity-based proteomics to reveal host-pathogen enzymatic dialogue in an animal model of infection.