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 | |
| Publication status | Published - Nov 25 2015 |
| Externally published | Yes |
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Cite this
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
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TY - JOUR
T1 - Phenotypic and genomic comparisons of highly vancomycin-resistant Staphylococcus aureus strains developed from multiple clinical MRSA strains by in vitro mutagenesis
AU - Ishii, Kenichi
AU - Tabuchi, Fumiaki
AU - Matsuo, Miki
AU - Tatsuno, Keita
AU - Sato, Tomoaki
AU - Okazaki, Mitsuhiro
AU - Hamamoto, Hiroshi
AU - Matsumoto, Yasuhiko
AU - Kaito, Chikara
AU - Aoyagi, Tetsuji
AU - Hiramatsu, Keiichi
AU - Kaku, Mitsuo
AU - Moriya, Kyoji
AU - Sekimizu, Kazuhisa
PY - 2015/11/25
Y1 - 2015/11/25
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84948169330&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84948169330&partnerID=8YFLogxK
U2 - 10.1038/srep17092
DO - 10.1038/srep17092
M3 - Article
C2 - 26603341
AN - SCOPUS:84948169330
VL - 5
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
M1 - 17092
ER -