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

November 9, 2021

Title

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

Author

Hiroshi Hamamoto, Suresh Panthee, Atmika Paudel, Kenichi Ishii, Jyunichi Ishii, Jyunichiro Yasukawa, Jie Su, Atsushi Miyashita, Hiroaki Itoh, Kotaro Tokumoto, Masayuki Inoue & Kazuhisa Sekimizu

Year

2021

Journal

Nature Communications

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.

Instrument

FP-6200

Keywords

Lysocin E, antibiotic activity,