Phenotypic and genomic comparisons of highly vancomycin-resistant Staphylococcus aureus strains developed from multiple clinical MRSA strains by in vitro mutagenesis

Kenichi Ishii; Fumiaki Tabuchi; Miki Matsuo; Keita Tatsuno; Tomoaki Sato; Mitsuhiro Okazaki; Hiroshi Hamamoto; Yasuhiko Matsumoto; Chikara Kaito; Tetsuji Aoyagi; Keiichi Hiramatsu; Mitsuo Kaku; Kyoji Moriya; Kazuhisa Sekimizu

doi:10.1038/srep17092

Phenotypic and genomic comparisons of highly vancomycin-resistant Staphylococcus aureus strains developed from multiple clinical MRSA strains by in vitro mutagenesis

Kenichi Ishii, Fumiaki Tabuchi, Miki Matsuo, Keita Tatsuno, Tomoaki Sato, Mitsuhiro Okazaki, Hiroshi Hamamoto, Yasuhiko Matsumoto, Chikara Kaito, Tetsuji Aoyagi, Keiichi Hiramatsu, Mitsuo Kaku, Kyoji Moriya, Kazuhisa Sekimizu

Research output: Contribution to journal › Article

12 Citations (Scopus)

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.

Original language	English
Article number	17092
Journal	Scientific reports
Volume	5
DOIs	https://doi.org/10.1038/srep17092
Publication status	Published - Nov 25 2015
Externally published	Yes

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Ishii, K., Tabuchi, F., Matsuo, M., Tatsuno, K., Sato, T., Okazaki, M., Hamamoto, H., Matsumoto, Y., Kaito, C., Aoyagi, T., Hiramatsu, K., Kaku, M., Moriya, K., & Sekimizu, K. (2015). Phenotypic and genomic comparisons of highly vancomycin-resistant Staphylococcus aureus strains developed from multiple clinical MRSA strains by in vitro mutagenesis. Scientific reports, 5, [17092]. https://doi.org/10.1038/srep17092

Phenotypic and genomic comparisons of highly vancomycin-resistant Staphylococcus aureus strains developed from multiple clinical MRSA strains by in vitro mutagenesis. / Ishii, Kenichi; Tabuchi, Fumiaki; Matsuo, Miki; Tatsuno, Keita; Sato, Tomoaki; Okazaki, Mitsuhiro; Hamamoto, Hiroshi; Matsumoto, Yasuhiko; Kaito, Chikara; Aoyagi, Tetsuji; Hiramatsu, Keiichi; Kaku, Mitsuo; Moriya, Kyoji; Sekimizu, Kazuhisa.

In: Scientific reports, Vol. 5, 17092, 25.11.2015.

Research output: Contribution to journal › Article

Ishii, K, Tabuchi, F, Matsuo, M, Tatsuno, K, Sato, T, Okazaki, M, Hamamoto, H, Matsumoto, Y, Kaito, C, Aoyagi, T, Hiramatsu, K, Kaku, M, Moriya, K & Sekimizu, K 2015, 'Phenotypic and genomic comparisons of highly vancomycin-resistant Staphylococcus aureus strains developed from multiple clinical MRSA strains by in vitro mutagenesis', Scientific reports, vol. 5, 17092. https://doi.org/10.1038/srep17092

Ishii, Kenichi ; Tabuchi, Fumiaki ; Matsuo, Miki ; Tatsuno, Keita ; Sato, Tomoaki ; Okazaki, Mitsuhiro ; Hamamoto, Hiroshi ; Matsumoto, Yasuhiko ; Kaito, Chikara ; Aoyagi, Tetsuji ; Hiramatsu, Keiichi ; Kaku, Mitsuo ; Moriya, Kyoji ; Sekimizu, Kazuhisa. / Phenotypic and genomic comparisons of highly vancomycin-resistant Staphylococcus aureus strains developed from multiple clinical MRSA strains by in vitro mutagenesis. In: Scientific reports. 2015 ; Vol. 5.

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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.",

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AU - Sato, Tomoaki

AU - Okazaki, Mitsuhiro

AU - Hamamoto, Hiroshi

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AU - Aoyagi, Tetsuji

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AU - Kaku, Mitsuo

AU - Moriya, Kyoji

AU - Sekimizu, Kazuhisa

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