Histone H1 kills MRSA.

IF 7.5 1区生物学 Q1 CELL BIOLOGY

Cell reports Pub Date : 2024-11-13 DOI:10.1016/j.celrep.2024.114969

Gerben Marsman, Xuhui Zheng, Dora Čerina, Keenan A Lacey, Menghan Liu, Daniel Humme, Christian Goosmann, Volker Brinkmann, C J Harbort, Victor J Torres, Arturo Zychlinsky

引用次数: 0

Abstract

The antimicrobial activity of histones was discovered in the 1940s, but their mechanism of action is not fully known. Here we show that methicillin-resistant Staphylococcus aureus (MRSA) is susceptible to histone H1 (H1), even in the presence of divalent cations and serum. Through selective evolution and a genome-wide screen of a transposon library, as well as physiological and pharmacological experiments, we elucidated how H1 kills MRSA. We show that H1 first binds to wall teichoic acids with high affinity. Once bound, H1 requires a potentiated membrane and a metabolically active bacterium to permeabilize the membrane and enter the cell. Upon entry, H1 accumulates intracellularly, in close association with the bacterial DNA. Of note, anti-H1 antibodies inhibit neutrophil extracellular trap killing of MRSA. Moreover, H1 colocalizes with bacterial DNA in abscess samples of MRSA-infected patients, suggesting a role for H1 in combating MRSA in vivo.

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组蛋白 H1 能杀死 MRSA。

组蛋白的抗菌活性于 20 世纪 40 年代被发现，但其作用机制尚未完全清楚。在这里，我们发现耐甲氧西林金黄色葡萄球菌（MRSA）对组蛋白 H1（H1）具有敏感性，即使在二价阳离子和血清存在的情况下也是如此。通过选择性进化、转座子文库的全基因组筛选以及生理学和药理学实验，我们阐明了 H1 如何杀死 MRSA。我们发现，H1 首先与菌壁茶酸结合，具有很高的亲和力。一旦与之结合，H1 就需要一个增效膜和一个代谢活跃的细菌来渗透膜并进入细胞。进入细胞后，H1 在细胞内积聚，与细菌 DNA 紧密结合。值得注意的是，抗 H1 抗体会抑制中性粒细胞胞外捕获器对 MRSA 的杀伤。此外，在MRSA感染患者的脓肿样本中，H1与细菌DNA共聚焦，这表明H1在体内抗击MRSA的作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell reports CELL BIOLOGY-

CiteScore

13.80

自引率

1.10%

发文量

1305

审稿时长

77 days

期刊介绍： Cell Reports publishes high-quality research across the life sciences and focuses on new biological insight as its primary criterion for publication. The journal offers three primary article types: Reports, which are shorter single-point articles, research articles, which are longer and provide deeper mechanistic insights, and resources, which highlight significant technical advances or major informational datasets that contribute to biological advances. Reviews covering recent literature in emerging and active fields are also accepted. The Cell Reports Portfolio includes gold open-access journals that cover life, medical, and physical sciences, and its mission is to make cutting-edge research and methodologies available to a wide readership. The journal's professional in-house editors work closely with authors, reviewers, and the scientific advisory board, which consists of current and future leaders in their respective fields. The advisory board guides the scope, content, and quality of the journal, but editorial decisions are independently made by the in-house scientific editors of Cell Reports.