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简化的铜防御机制使百日咳博德特氏菌依赖于定制操纵子。

Streamlined copper defenses make Bordetella pertussis reliant on custom-made operon.

作者信息

Rivera-Millot Alex, Slupek Stéphanie, Chatagnon Jonathan, Roy Gauthier, Saliou Jean-Michel, Billon Gabriel, Alaimo Véronique, Hot David, Salomé-Desnoulez Sophie, Locht Camille, Antoine Rudy, Jacob-Dubuisson Françoise

机构信息

Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019- UMR 9017-CIIL-Center for Infection and Immunity of Lille, Lille, France.

Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, US 41 - UMS 2014 - PLBS, F-59000, Lille, France.

出版信息

Commun Biol. 2021 Jan 8;4(1):46. doi: 10.1038/s42003-020-01580-2.

DOI:10.1038/s42003-020-01580-2
PMID:33420409
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7794356/
Abstract

Copper is both essential and toxic to living beings, which tightly controls its intracellular concentration. At the host-pathogen interface, copper is used by phagocytic cells to kill invading microorganisms. We investigated copper homeostasis in Bordetella pertussis, which lives in the human respiratory mucosa and has no environmental reservoir. B. pertussis has considerably streamlined copper homeostasis mechanisms relative to other Gram-negative bacteria. Its single remaining defense line consists of a metallochaperone diverted for copper passivation, CopZ, and two peroxide detoxification enzymes, PrxGrx and GorB, which together fight stresses encountered in phagocytic cells. Those proteins are encoded by an original, composite operon assembled in an environmental ancestor, which is under sensitive control by copper. This system appears to contribute to persistent infection in the nasal cavity of B. pertussis-infected mice. Combining responses to co-occurring stresses in a tailored operon reveals a strategy adopted by a host-restricted pathogen to optimize survival at minimal energy expenditure.

摘要

铜对于生物来说既是必需的，也是有毒的，生物会严格控制其细胞内的浓度。在宿主与病原体的界面处，吞噬细胞利用铜来杀死入侵的微生物。我们研究了百日咳博德特氏菌中的铜稳态，该菌生活在人类呼吸道黏膜中，没有环境储存库。相对于其他革兰氏阴性菌，百日咳博德特氏菌的铜稳态机制已大幅简化。其仅存的一条防御线由一种用于铜钝化的金属伴侣蛋白CopZ以及两种过氧化物解毒酶PrxGrx和GorB组成，它们共同应对吞噬细胞中遇到的压力。这些蛋白质由一个在环境祖先中组装的原始复合操纵子编码，该操纵子受铜的敏感调控。这个系统似乎有助于百日咳博德特氏菌感染小鼠鼻腔中的持续感染。在一个定制的操纵子中组合对同时出现的压力的反应，揭示了一种宿主限制性病原体为以最小能量消耗优化生存而采用的策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a28/7794356/81f1ecf0ca14/42003_2020_1580_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a28/7794356/5b1c66369e96/42003_2020_1580_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a28/7794356/76470a4e0a9c/42003_2020_1580_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a28/7794356/0f71e88b395e/42003_2020_1580_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a28/7794356/5d8e68b9c9c2/42003_2020_1580_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a28/7794356/93d670769b4b/42003_2020_1580_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a28/7794356/9fe91798b899/42003_2020_1580_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a28/7794356/81f1ecf0ca14/42003_2020_1580_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a28/7794356/5b1c66369e96/42003_2020_1580_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a28/7794356/76470a4e0a9c/42003_2020_1580_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a28/7794356/0f71e88b395e/42003_2020_1580_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a28/7794356/5d8e68b9c9c2/42003_2020_1580_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a28/7794356/93d670769b4b/42003_2020_1580_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a28/7794356/9fe91798b899/42003_2020_1580_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a28/7794356/81f1ecf0ca14/42003_2020_1580_Fig7_HTML.jpg

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Front Microbiol. 2019 Dec 11;10:2839. doi: 10.3389/fmicb.2019.02839. eCollection 2019.
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Relationships Between Copper-Related Proteomes and Lifestyles in β Proteobacteria.β-变形菌纲中与铜相关的蛋白质组与生活方式之间的关系
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Metals as phagocyte antimicrobial effectors.金属作为吞噬细胞的抗菌效应因子。
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