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

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 metha...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
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Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4658547/
https://www.ncbi.nlm.nih.gov/pubmed/26603341
http://dx.doi.org/10.1038/srep17092
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author 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
author_facet 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
author_sort Ishii, Kenichi
collection PubMed
description 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 = 32 μg/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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spelling pubmed-46585472015-11-30 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 Sci Rep Article 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 = 32 μg/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. Nature Publishing Group 2015-11-25 /pmc/articles/PMC4658547/ /pubmed/26603341 http://dx.doi.org/10.1038/srep17092 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
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
title Phenotypic and genomic comparisons of highly vancomycin-resistant Staphylococcus aureus strains developed from multiple clinical MRSA strains by in vitro mutagenesis
title_full Phenotypic and genomic comparisons of highly vancomycin-resistant Staphylococcus aureus strains developed from multiple clinical MRSA strains by in vitro mutagenesis
title_fullStr Phenotypic and genomic comparisons of highly vancomycin-resistant Staphylococcus aureus strains developed from multiple clinical MRSA strains by in vitro mutagenesis
title_full_unstemmed Phenotypic and genomic comparisons of highly vancomycin-resistant Staphylococcus aureus strains developed from multiple clinical MRSA strains by in vitro mutagenesis
title_short Phenotypic and genomic comparisons of highly vancomycin-resistant Staphylococcus aureus strains developed from multiple clinical MRSA strains by in vitro mutagenesis
title_sort phenotypic and genomic comparisons of highly vancomycin-resistant staphylococcus aureus strains developed from multiple clinical mrsa strains by in vitro mutagenesis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4658547/
https://www.ncbi.nlm.nih.gov/pubmed/26603341
http://dx.doi.org/10.1038/srep17092
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