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一个大规模的I型CBASS抗菌幕识别了体前头蛋白酶作为免疫激活和逃避的关键决定因素

Desmond Richmond-Buccola¹, Samuel J Hobbs¹, Jasmine M Garcia²

¹Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.

Cell host & microbe

|June 25, 2024

概括

循环寡核酸基信号系统 (CBASS) 保护细菌免受菌体的侵害. 菌体通过突变组装蛋白来逃避这种抗病毒防御,这表明病毒蛋白识别激活了CBASS.

科学领域:

微生物学微生物学
免疫学免疫学免疫学
分子生物学分子生物学

背景情况:

循环寡核酸基信号系统 (CBASS) 是一种细菌抗病毒防御机制.
在进化过程中,CBASS与人类cGAS-STING天生的免疫路径有关.
对于CBASS激活的精确分子触发器仍然在很大程度上是未知的.

研究的目的:

研究激活I型CBASS系统的分子线索.
了解细菌和菌体在CBASS-菌体军备竞赛中如何相互作用.
为了确定菌体规避CBASS介导免疫力的策略.

主要方法:

进行了975个I型CBASS操作-菌体挑战的大型屏幕.
基因分析被用来识别赋予菌体耐药性的突变.
进行了蛋白相互作用研究以阐明分子机制.

主要成果:

通过它们的cGAS/DncV类核基转移酶 (CD-NTases) 和效应体来定义的独特的I型CBASS操作子,显示出特定的菌体限制模式.
一些CD-NTase酶需要C端的AGS-C免疫球蛋白 (Ig) 类折叠来进行抗病毒活性.
菌体通过获得virion组装蛋白中的突变来进化耐药性,耐药性是操作特异的.
菌体 Bas13 前头蛋白酶被证明与 EcCdnD12 相互作用,并诱导依赖 CBASS 的生长停止.

结论:

体病毒组合蛋白是I型CBASS免疫逃避的关键决定因素.
识别病毒蛋白质是激活细菌中的cGAS类酶的可能机制.
这项研究提供了细菌免疫和病毒反防御策略的共同演变的见解.

关键词:

这是CBASS,是CBASS.这就是CD-NTase.抗菌体防御系统的抗菌体防御病毒组合的病毒组合.病毒性免疫逃避病毒性免疫逃避

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