Histone H1 kills MRSA

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.

Authors

Institutions

Publication Details

Journal
Cell Reports
Published
2024-11-01
DOI
https://doi.org/10.1016/j.celrep.2024.114969
Citations
6
Primary Topic
Antimicrobial Peptides and Activities
Type
article
Field-Weighted Citation Impact
2.07

Funders

Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Histone H1 kills MRSA

Dora Čerina, Christopher J. Harbort, Menghan Liu, Daniel Humme et al.
6 citations
Cell Reports
Antimicrobial Peptides and Activities
2.07
article

Histone H1 kills MRSA

Dora Čerina, Christopher J. Harbort, Menghan Liu, Daniel Humme, Christian Goosmann, Victor J. Torres, Xuhui Zheng, Keenan A. Lacey, Gerben Marsman, Volker Brinkmann, Arturo Zychlinsky
article en
6 citations

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.

Cell ReportsVol. 43(11)
St. Jude Children's Research Hospital (US), Humboldt-Universität zu Berlin (DE), Max Planck Institute for Infection Biology (DE), New York University (US), Freie Universität Berlin (DE), Charité - Universitätsmedizin Berlin (DE)
Burroughs Wellcome Fund, Max-Planck-Gesellschaft, National Institutes of Health, National Cancer Institute, National Institute of Allergy and Infectious Diseases
Openalex Percentile: Top 13%
Antimicrobial Peptides and Activities
2.07
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.