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Altered genomic methylation promotes Staphylococcus aureus persistence in hospital environment

Author

Listed:
  • Yuriko Yamazaki

    (Chiba University Graduate School of Medicine
    Osaka University
    Osaka University Graduate School of Medicine)

  • Tomoka Ito

    (Osaka University Graduate School of Medicine)

  • Seitaro Nakagawa

    (Chiba University Graduate School of Medicine
    University of Michigan Medical School)

  • Takashi Sugihira

    (Osaka University Graduate School of Medicine)

  • Chinami Kurita-Tachibana

    (Osaka University)

  • Amer E. Villaruz

    (Bethesda)

  • Kensuke Ishiguro

    (The University of Tokyo)

  • Barbora Salcman

    (Osaka University)

  • Shuo Li

    (Osaka University)

  • Sanami Takada

    (Chiba University Graduate School of Medicine)

  • Naohiro Inohara

    (University of Michigan Medical School)

  • Yoko Kusuya

    (Chiba University)

  • Aki Shibata

    (Chiba University)

  • Masakazu Tamai

    (Osaka University Graduate School of Medicine)

  • Reika Aoyama

    (Osaka University Graduate School of Medicine)

  • Kanako Inoue

    (Osaka University)

  • Shota Murata

    (Chiba University Hospital)

  • Kazuyuki Matsushita

    (Chiba University Hospital)

  • Akiko Miyabe

    (Chiba University Hospital)

  • Toshibumi Taniguchi

    (Chiba University Hospital)

  • Hidetoshi Igari

    (Chiba University Hospital)

  • Naruhiko Ishiwada

    (Chiba University)

  • Masateru Taniguchi

    (Osaka University)

  • Taka-Aki Nakada

    (Chiba University Graduate School of Medicine)

  • Hiroyuki Matsue

    (Chiba University Graduate School of Medicine)

  • Manabu Fujimoto

    (Osaka University Graduate School of Medicine
    Osaka University)

  • Haruka Hishiki

    (Chiba University Graduate School of Medicine)

  • Yoshiteru Osone

    (Chiba University Graduate School of Medicine)

  • Hiromichi Hamada

    (Chiba University Graduate School of Medicine)

  • Naoki Shimojo

    (Chiba University Graduate School of Medicine
    Chiba University)

  • Tsutomu Suzuki

    (The University of Tokyo)

  • Michael Otto

    (Bethesda)

  • Gabriel Núñez

    (University of Michigan Medical School)

  • Hiroki Takahashi

    (Chiba University
    Chiba University
    Chiba University)

  • Akiko Takaya

    (Chiba University
    Chiba University
    Chiba University)

  • Yuumi Nakamura

    (Osaka University
    Osaka University Graduate School of Medicine
    Osaka University)

Abstract

Staphylococcus aureus can cause outbreaks and becomes multi-drug resistant through gene mutations and acquiring resistance genes. However, why S. aureus easily adapts to hospital environments, promoting resistance and recurrent infections, remains unknown. Here we show that a specific S. aureus lineage evolved from a clone that expresses the accessory gene regulator (Agr) system to subclones that reversibly suppressed Agr and caused an outbreak in the hospital setting. S. aureus with flexible Agr regulation shows increased ability to acquire antibiotic-resistant plasmids, escape host immunity, and colonize mice. Bacteria with flexible Agr regulation shows altered cytosine genomic methylation, including the decreased 5mC methylation in transcriptional regulator genes (pcrA and rpsD), compared to strains with normal Agr expression patterns. In this work, we discover how altered genomic methylation promotes flexible Agr regulation which is associated with persistent pathogen colonization in the hospital environment.

Suggested Citation

  • Yuriko Yamazaki & Tomoka Ito & Seitaro Nakagawa & Takashi Sugihira & Chinami Kurita-Tachibana & Amer E. Villaruz & Kensuke Ishiguro & Barbora Salcman & Shuo Li & Sanami Takada & Naohiro Inohara & Yoko, 2024. "Altered genomic methylation promotes Staphylococcus aureus persistence in hospital environment," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-54033-3
    DOI: 10.1038/s41467-024-54033-3
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    References listed on IDEAS

    as
    1. Yuumi Nakamura & Jon Oscherwitz & Kemp B. Cease & Susana M. Chan & Raul Muñoz-Planillo & Mizuho Hasegawa & Amer E. Villaruz & Gordon Y. C. Cheung & Martin J. McGavin & Jeffrey B. Travers & Michael Ott, 2013. "Staphylococcus δ-toxin induces allergic skin disease by activating mast cells," Nature, Nature, vol. 503(7476), pages 397-401, November.
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