Serum apolipoprotein A-I potentiates the therapeutic efficacy of lysocin E against Staphylococcus aureus

Hiroshi Hamamoto, Suresh Panthee, Atmika Paudel, Kenichi Ishii, Jyunichiro Yasukawa, Jie Su, Atsushi Miyashita, Hiroaki Itoh, Kotaro Tokumoto, Masayuki Inoue and Kazuhisa Sekimizu ()
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Hiroshi Hamamoto: Teikyo University Institute of Medical Mycology
Suresh Panthee: Teikyo University
Atmika Paudel: Hokkaido University
Kenichi Ishii: The University of Tokyo
Jyunichiro Yasukawa: Doshisha Women’s College of Liberal Arts
Jie Su: National Marine Environmental Monitoring Center
Atsushi Miyashita: Teikyo University Institute of Medical Mycology
Hiroaki Itoh: The University of Tokyo
Kotaro Tokumoto: The University of Tokyo
Masayuki Inoue: The University of Tokyo
Kazuhisa Sekimizu: Teikyo University

Nature Communications, 2021, vol. 12, issue 1, 1-10

Abstract: Abstract Lysocin E is a lipopeptide with antibiotic activity against methicillin-resistant Staphylococcus aureus. For unclear reasons, the antibacterial activity of lysocin E in a mouse systemic infection model is higher than expected from in vitro results, and the in vitro activity is enhanced by addition of bovine serum. Here, we confirm that serum from various species, including humans, increases lysocin E antimicrobial activity, and identify apolipoprotein A-I (ApoA-I) as an enhancing factor. ApoA-I increases the antibacterial activity of lysocin E when added in vitro, and the antibiotic displays reduced activity in ApoA-I gene knockout mice. Binding of ApoA-I to lysocin E is enhanced by lipid II, a cell-wall synthesis precursor found in the bacterial membrane. Thus, the antimicrobial activity of lysocin E is potentiated through interactions with host serum proteins and microbial components.

Date: 2021
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DOI: 10.1038/s41467-021-26702-0

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