| Autor: |
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 |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
Cell Reports, Vol 43, Iss 11, Pp 114969- (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2211-1247 |
| DOI: |
10.1016/j.celrep.2024.114969 |
| Popis: |
Summary: 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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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