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

Author

Listed:
  • Hiroshi Hamamoto

    (Teikyo University Institute of Medical Mycology
    Teikyo University)

  • 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
    Genome Pharmaceuticals Institute, Ltd)

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.

Suggested Citation

  • Hiroshi Hamamoto & Suresh Panthee & Atmika Paudel & Kenichi Ishii & Jyunichiro Yasukawa & Jie Su & Atsushi Miyashita & Hiroaki Itoh & Kotaro Tokumoto & Masayuki Inoue & Kazuhisa Sekimizu, 2021. "Serum apolipoprotein A-I potentiates the therapeutic efficacy of lysocin E against Staphylococcus aureus," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26702-0
    DOI: 10.1038/s41467-021-26702-0
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    References listed on IDEAS

    as
    1. Losee L. Ling & Tanja Schneider & Aaron J. Peoples & Amy L. Spoering & Ina Engels & Brian P. Conlon & Anna Mueller & Till F. Schäberle & Dallas E. Hughes & Slava Epstein & Michael Jones & Linos Lazari, 2015. "A new antibiotic kills pathogens without detectable resistance," Nature, Nature, vol. 517(7535), pages 455-459, January.
    2. Hiroaki Itoh & Kotaro Tokumoto & Takuya Kaji & Atmika Paudel & Suresh Panthee & Hiroshi Hamamoto & Kazuhisa Sekimizu & Masayuki Inoue, 2019. "Development of a high-throughput strategy for discovery of potent analogues of antibiotic lysocin E," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    3. Losee L. Ling & Tanja Schneider & Aaron J. Peoples & Amy L. Spoering & Ina Engels & Brian P. Conlon & Anna Mueller & Till F. Schäberle & Dallas E. Hughes & Slava Epstein & Michael Jones & Linos Lazari, 2015. "Erratum: A new antibiotic kills pathogens without detectable resistance," Nature, Nature, vol. 520(7547), pages 388-388, April.
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