Altered genomic methylation promotes Staphylococcus aureus persistence in hospital environment
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.
Authors
- Tsutomu Suzuki (ORCID: https://orcid.org/0000-0002-9731-1731)
- Kanako Inoue (ORCID: https://orcid.org/0000-0002-3691-263X)
- Manabu Fujimoto (ORCID: https://orcid.org/0000-0002-3062-4872)
- Akiko Takaya (ORCID: https://orcid.org/0000-0003-1726-7150)
- Aki Shibata (ORCID: https://orcid.org/0000-0002-8280-869X)
- Yuriko Yamazaki (ORCID: https://orcid.org/0000-0002-4026-8306)
- Masateru Taniguchi (ORCID: https://orcid.org/0000-0002-0338-8755)
- Masakazu Tamai (ORCID: https://orcid.org/0000-0002-0120-4828)
- Hiromichi Hamada (ORCID: https://orcid.org/0000-0002-8990-5265)
- Seitaro Nakagawa (ORCID: https://orcid.org/0000-0002-1119-0001)
- Taka‐aki Nakada (ORCID: https://orcid.org/0000-0002-4480-556X)
- Yuumi Nakamura (ORCID: https://orcid.org/0000-0001-6256-8302)
- Reika Aoyama (ORCID: https://orcid.org/0000-0002-0703-3281)
- Naoki Shimojo (ORCID: https://orcid.org/0000-0002-8076-0493)
- Gabriel Núñez (ORCID: https://orcid.org/0000-0002-6529-2695)
- Tomoka Ito (ORCID: https://orcid.org/0009-0001-7281-6928)
- Kazuyuki Matsushita (ORCID: https://orcid.org/0000-0001-6742-0761)
- Naruhiko Ishiwada (ORCID: https://orcid.org/0000-0002-7508-1330)
- Yoshiteru Osone (ORCID: https://orcid.org/0000-0001-5712-7019)
- Michaël Otto (ORCID: https://orcid.org/0000-0002-2222-4115)
- Hiroyuki Matsue (ORCID: https://orcid.org/0000-0002-5269-4046)
- Sanami Takada (ORCID: https://orcid.org/0000-0002-3357-3185)
- Haruka Hishiki
- Barbora Salcman
- Shota Murata
- Kensuke Ishiguro (ORCID: https://orcid.org/0000-0001-6651-1960)
- Yoko Kusuya (ORCID: https://orcid.org/0000-0002-5724-487X)
- Toshibumi Taniguchi (ORCID: https://orcid.org/0000-0002-7732-9870)
- Amer E. Villaruz
- Hidetoshi Igari (ORCID: https://orcid.org/0000-0001-7754-3458)
- Takashi Sugihira
- Naohiro Inohara (ORCID: https://orcid.org/0000-0002-4215-9349)
- Akiko Miyabe
- Hiroki Takahashi (ORCID: https://orcid.org/0000-0001-5627-1035)
- Shuo Li (ORCID: https://orcid.org/0000-0002-0811-5166)
- Chinami Kurita-Tachibana
Institutions
- National Institutes of Health (US)
- Chiba University (JP)
- University of Michigan (US)
- Chiba University Hospital (JP)
- National Institute of Allergy and Infectious Diseases (US)
- The University of Tokyo (JP)
- The University of Osaka (JP)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-11-07
- DOI
- https://doi.org/10.1038/s41467-024-54033-3
- Citations
- 11
- Primary Topic
- Antimicrobial Resistance in Staphylococcus
- Type
- article
- Field-Weighted Citation Impact
- 4.28
Funders
- Division of Intramural Research, National Institute of Allergy and Infectious Diseases
- Uehara Memorial Foundation
- Japan Agency for Medical Research and Development
- Environmental Restoration and Conservation Agency
- Ministry of Education, Culture, Sports, Science and Technology
- Chiba University
- Japan Society for the Promotion of Science
- National Institute of Allergy and Infectious Diseases
- Institute of Genetics
- Core Research for Evolutional Science and Technology