Histone H1 kills MRSA

• DOI: 10.1016/j.celrep.2024.114969
• Publication Date: 2024-11-14T02:33:09Z
• Authors: 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
• Keywords: 0301 basic medicine; 03 medical and health sciences; QH301-705.5; CP: Microbiology; Biology (General)

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