Altered genomic methylation promotes Staphylococcus aureus persistence in hospital environment

Altered genomic methylation promotes Staphylococcus aureus persistence in hospital environment

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. au...

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Main Authors: 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
Format: Article
Language:English
Published: Nature Portfolio 2024-11-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-024-54033-3
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Summary: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.
ISSN:2041-1723

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