@article{3d90eec6a03341aeb006803bc40d8efc,
title = "Phenotypic and genomic comparisons of highly vancomycin-resistant Staphylococcus aureus strains developed from multiple clinical MRSA strains by in vitro mutagenesis",
abstract = "The development of vancomycin (VCM) resistance in Staphylococcus aureus threatens global health. Studies of the VCM-resistance mechanism and alternative therapeutic strategies are urgently needed. We mutagenized S. aureus laboratory strains and methicillin-resistant S. aureus (MRSA) with ethyl methanesulfonate, and isolated mutants that exhibited high resistance to VCM (minimum inhibitory concentration=32μg/ml). These VCM-resistant strains were sensitive to linezolid and rifampicin, and partly to arbekacin and daptomycin. Beta-lactams had synergistic effects with VCM against these mutants. VCM-resistant strains exhibited a 2-fold increase in the cell wall thickness. Several genes were commonly mutated among the highly VCM-resistant mutants. These findings suggest that MRSA has a potential to develop high VCM resistance with cell wall thickening by the accumulation of mutations.",
author = "Kenichi Ishii and Fumiaki Tabuchi and Miki Matsuo and Keita Tatsuno and Tomoaki Sato and Mitsuhiro Okazaki and Hiroshi Hamamoto and Yasuhiko Matsumoto and Chikara Kaito and Tetsuji Aoyagi and Keiichi Hiramatsu and Mitsuo Kaku and Kyoji Moriya and Kazuhisa Sekimizu",
note = "Funding Information: This study was supported by a grant from Genome Pharmaceuticals Institute Co., Ltd. to KS, KAKENHI grant number 26670043 (Grant-in-Aid for Challenging Exploratory Research to HH), and JSPS grant number 24-11042 (Grant-in-Aid for JSPS fellows to KI); and was supported in part by JSPS KAKENHI 24689008 (Grant-in-Aid for Young Scientists (A) to HH), and JST A-STEP (High-risk challenging type). We thank Dr. Takashi Sasaki for helpful discussion on genome-sequencing analysis, and for Mr. Mitsutaka Yoshida (Division of Ultrastructural Research, Juntendo University) for invaluable assistance in sample preparation and technical support of transmission electron microscopy. Publisher Copyright: {\textcopyright} 2015, Nature Publishing Group. All rights reserved.",
year = "2015",
month = nov,
day = "25",
doi = "10.1038/srep17092",
language = "English",
volume = "5",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
}