Functional and Structural Diversity of Bacterial Contact-Dependent Growth Inhibition Effectors.

Functional and Structural Diversity of Bacterial Contact-Dependent Growth Inhibition Effectors.
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DOI:
10.3389/fmolb.2022.866854
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发表时间:
2022
影响因子:
5
通讯作者:
--
中科院分区:
生物学3区
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--
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细菌生活在复杂的群落和环境中,争夺空间和营养。在它们的生态位栖息地内,细菌已经发展出各种细菌间机制来竞争和交流。其中一种机制是接触依赖性生长抑制(CDI)。 CDI 存在于许多革兰氏阴性细菌中,包括几种病原体。这些 CDI+ 细菌编码 CdiB/CdiA 双伙伴分泌系统,在接触时将抑制性毒素传递到邻近细胞中。毒素易位导致密切相关菌株的生长抑制,并为 CDI+ 细菌提供竞争优势。 CdiB 是一种外膜蛋白,将 CdiA 分泌到 CDI+ 细菌的表面。当 CdiA 与特定靶细胞受体相互作用时,CdiA 将其 C 末端毒素区域 (CdiA-CT) 传递到靶细胞中。 CdiA-CT 毒素蛋白表现出多种毒性功能,例如 DNase、RNase 或成孔毒素活性。 CDI+ 细菌还编码一种免疫蛋白 CdiI,该蛋白特异性结合并中和其同源 CdiA-CT,从而保护 CDI+ 细菌免受自身抑制。在革兰氏阴性细菌中,毒素/免疫 (CdiA-CT/CdiI) 对具有高度可变的序列和功能,预测有超过 130 个不同的毒素/免疫复合物家族。在这篇综述中,我们将讨论 CDI 表征方面取得的生化和结构进展。本综述将重点关注各种 CDI 毒素/免疫复合物结构及其独特的毒素功能。此外,我们将讨论有关靶细胞识别和毒素进入的最新研究,以及 CDI 位点新成员的发现。最后,我们将深入探讨如何利用这些不同的毒素/免疫复合物来对抗人类疾病。
Bacteria live in complex communities and environments, competing for space and nutrients. Within their niche habitats, bacteria have developed various inter-bacterial mechanisms to compete and communicate. One such mechanism is contact-dependent growth inhibition (CDI). CDI is found in many Gram-negative bacteria, including several pathogens. These CDI+ bacteria encode a CdiB/CdiA two-partner secretion system that delivers inhibitory toxins into neighboring cells upon contact. Toxin translocation results in the growth inhibition of closely related strains and provides a competitive advantage to the CDI+ bacteria. CdiB, an outer-membrane protein, secretes CdiA onto the surface of the CDI+ bacteria. When CdiA interacts with specific target-cell receptors, CdiA delivers its C-terminal toxin region (CdiA-CT) into the target-cell. CdiA-CT toxin proteins display a diverse range of toxic functions, such as DNase, RNase, or pore-forming toxin activity. CDI+ bacteria also encode an immunity protein, CdiI, that specifically binds and neutralizes its cognate CdiA-CT, protecting the CDI+ bacteria from auto-inhibition. In Gram-negative bacteria, toxin/immunity (CdiA-CT/CdiI) pairs have highly variable sequences and functions, with over 130 predicted divergent toxin/immunity complex families. In this review, we will discuss biochemical and structural advances made in the characterization of CDI. This review will focus on the diverse array of CDI toxin/immunity complex structures together with their distinct toxin functions. Additionally, we will discuss the most recent studies on target-cell recognition and toxin entry, along with the discovery of a new member of the CDI loci. Finally, we will offer insights into how these diverse toxin/immunity complexes could be harnessed to fight human diseases.
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