Nature Communications (Nov 2024)
Altered genomic methylation promotes Staphylococcus aureus persistence in hospital environment
- 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 Kusuya,
- Aki Shibata,
- Masakazu Tamai,
- Reika Aoyama,
- Kanako Inoue,
- Shota Murata,
- Kazuyuki Matsushita,
- Akiko Miyabe,
- Toshibumi Taniguchi,
- Hidetoshi Igari,
- Naruhiko Ishiwada,
- Masateru Taniguchi,
- Taka-Aki Nakada,
- Hiroyuki Matsue,
- Manabu Fujimoto,
- Haruka Hishiki,
- Yoshiteru Osone,
- Hiromichi Hamada,
- Naoki Shimojo,
- Tsutomu Suzuki,
- Michael Otto,
- Gabriel Núñez,
- Hiroki Takahashi,
- Akiko Takaya,
- Yuumi Nakamura
Affiliations
- Yuriko Yamazaki
- Department of Dermatology, Chiba University Graduate School of Medicine
- Tomoka Ito
- Department of Dermatology, Osaka University Graduate School of Medicine
- Seitaro Nakagawa
- Department of Dermatology, Chiba University Graduate School of Medicine
- Takashi Sugihira
- Department of Dermatology, Osaka University Graduate School of Medicine
- Chinami Kurita-Tachibana
- Cutaneous Allergy and Host Defense, Immunology Frontier Research Center, Osaka University
- Amer E. Villaruz
- Pathogen Molecular Genetics Section, Laboratory of Human Bacterial Pathogenesis, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda
- Kensuke Ishiguro
- Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo
- Barbora Salcman
- Cutaneous Allergy and Host Defense, Immunology Frontier Research Center, Osaka University
- Shuo Li
- Cutaneous Allergy and Host Defense, Immunology Frontier Research Center, Osaka University
- Sanami Takada
- Department of Dermatology, Chiba University Graduate School of Medicine
- Naohiro Inohara
- Department of Pathology and Rogel Cancer Center, University of Michigan Medical School
- Yoko Kusuya
- Medical Mycology Research Center, Chiba University
- Aki Shibata
- Department of Infection Control Science, Graduate School of Pharmaceutical Sciences, Chiba University
- Masakazu Tamai
- Department of Dermatology, Osaka University Graduate School of Medicine
- Reika Aoyama
- Department of Dermatology, Osaka University Graduate School of Medicine
- Kanako Inoue
- Research Center for Ultra-High Voltage Electron Microscopy, Osaka University
- Shota Murata
- Division of Clinical Laboratory, Chiba University Hospital
- Kazuyuki Matsushita
- Division of Clinical Laboratory, Chiba University Hospital
- Akiko Miyabe
- Division of Clinical Laboratory, Chiba University Hospital
- Toshibumi Taniguchi
- Division of Infection Control, Chiba University Hospital
- Hidetoshi Igari
- Division of Infection Control, Chiba University Hospital
- Naruhiko Ishiwada
- Department of Infectious Diseases, Medical Mycology Research Center, Chiba University
- Masateru Taniguchi
- Department of Bio-Nanotechnology, The Institute of Scientific and Industrial Research, Osaka University
- Taka-Aki Nakada
- Department of Emergency and Critical Care Medicine, Chiba University Graduate School of Medicine
- Hiroyuki Matsue
- Department of Dermatology, Chiba University Graduate School of Medicine
- Manabu Fujimoto
- Department of Dermatology, Osaka University Graduate School of Medicine
- Haruka Hishiki
- Department of Pediatrics, Chiba University Graduate School of Medicine
- Yoshiteru Osone
- Department of Pediatrics, Chiba University Graduate School of Medicine
- Hiromichi Hamada
- Department of Pediatrics, Chiba University Graduate School of Medicine
- Naoki Shimojo
- Department of Pediatrics, Chiba University Graduate School of Medicine
- Tsutomu Suzuki
- Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo
- Michael Otto
- Pathogen Molecular Genetics Section, Laboratory of Human Bacterial Pathogenesis, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda
- Gabriel Núñez
- Department of Pathology and Rogel Cancer Center, University of Michigan Medical School
- Hiroki Takahashi
- Medical Mycology Research Center, Chiba University
- Akiko Takaya
- Medical Mycology Research Center, Chiba University
- Yuumi Nakamura
- Cutaneous Allergy and Host Defense, Immunology Frontier Research Center, Osaka University
- DOI
- https://doi.org/10.1038/s41467-024-54033-3
- Journal volume & issue
-
Vol. 15,
no. 1
pp. 1 – 15
Abstract
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.
