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Staphylococcus aureus virulence attenuation and immune clearance mediated by a phage lysin‐derived protein
Author(s) -
Yang Hang,
Xu Jingjing,
Li Wuyou,
Wang Shujuan,
Li Junhua,
Yu Junping,
Li Yuhong,
Wei Hongping
Publication year - 2018
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201798045
Subject(s) - biology , lysin , virulence , microbiology and biotechnology , staphylococcus aureus , immune system , bacteriophage , bacterial protein , staphylococcal infections , bacteria , virology , genetics , gene , escherichia coli
New anti‐infective approaches are much needed to control multi‐drug‐resistant ( MDR ) pathogens, such as methicillin‐resistant Staphylococcus aureus ( MRSA ). Here, we found for the first time that a recombinant protein derived from the cell wall binding domain ( CBD ) of the bacteriophage lysin PlyV12, designated as V12 CBD , could attenuate S. aureus virulence and enhance host immune defenses via multiple manners. After binding with V12 CBD , S. aureus became less invasive to epithelial cells and more susceptible to macrophage killing. The expressions of multiple important virulence genes of S. aureus were reduced 2.4‐ to 23.4‐fold as response to V12 CBD . More significantly, V12 CBD could activate macrophages through NF ‐κB pathway and enhance phagocytosis against S. aureus . As a result, good protections of the mice from MRSA infections were achieved in therapeutic and prophylactic models. These unique functions of V12 CBD would render it a novel alternative molecule to control MDR S. aureus infections.