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Single nucleotide polymorphism leads to daptomycin resistance causing amino acid substitution—T345I in MprF of clinically isolated MRSA strains

Daptomycin (DAP) is one of the most potent antibiotics used for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections. Due to an increase in its administration for combating MRSA infections, DAP non-susceptible (DAP-NS) MRSA strains have recently been reported in clinical se...

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Autores principales: Nakamura, Masaki, Kawada, Hayato, Uchida, Hiroki, Takagi, Yusuke, Obata, Shuichi, Eda, Ryotaro, Hanaki, Hideaki, Kitasato, Hidero
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7822245/
https://www.ncbi.nlm.nih.gov/pubmed/33481910
http://dx.doi.org/10.1371/journal.pone.0245732
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author Nakamura, Masaki
Kawada, Hayato
Uchida, Hiroki
Takagi, Yusuke
Obata, Shuichi
Eda, Ryotaro
Hanaki, Hideaki
Kitasato, Hidero
author_facet Nakamura, Masaki
Kawada, Hayato
Uchida, Hiroki
Takagi, Yusuke
Obata, Shuichi
Eda, Ryotaro
Hanaki, Hideaki
Kitasato, Hidero
author_sort Nakamura, Masaki
collection PubMed
description Daptomycin (DAP) is one of the most potent antibiotics used for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections. Due to an increase in its administration for combating MRSA infections, DAP non-susceptible (DAP-NS) MRSA strains have recently been reported in clinical settings. The presence of single nucleotide polymorphisms (SNPs) in the multiple peptide resistance factor (mprF) gene is the most frequently reported cause for the evolution of DAP-NS MRSA strains; however, there are some variations of SNPs that could lead to DAP-NS. In this study, we used two clinical MRSA strains, including DAP susceptible (DAP-S) and DAP-NS, isolated from the same patient at different time points. We introduced T345I SNP to mprF of the DAP-S MRSA strain using the gene exchange method with pIMAY vector. Further, we investigated the phenotype of the mutant strain, including drug susceptibility, cell surface positive charge, and growth speed. The mutant strain exhibited (i) resistance to DAP, (ii) up-regulation of positive surface charge, (iii) slower growth speed, and (iv) thickened cell walls. Hence, the SNP in mprF may have caused an up-regulation in MprF function, with a subsequent increase in positive surface charge. Cumulatively, these results demonstrated that the T345I amino acid substitution in mprF represents one of the primary causes of DAP-NS in MRSA strains.
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spelling pubmed-78222452021-01-29 Single nucleotide polymorphism leads to daptomycin resistance causing amino acid substitution—T345I in MprF of clinically isolated MRSA strains Nakamura, Masaki Kawada, Hayato Uchida, Hiroki Takagi, Yusuke Obata, Shuichi Eda, Ryotaro Hanaki, Hideaki Kitasato, Hidero PLoS One Research Article Daptomycin (DAP) is one of the most potent antibiotics used for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections. Due to an increase in its administration for combating MRSA infections, DAP non-susceptible (DAP-NS) MRSA strains have recently been reported in clinical settings. The presence of single nucleotide polymorphisms (SNPs) in the multiple peptide resistance factor (mprF) gene is the most frequently reported cause for the evolution of DAP-NS MRSA strains; however, there are some variations of SNPs that could lead to DAP-NS. In this study, we used two clinical MRSA strains, including DAP susceptible (DAP-S) and DAP-NS, isolated from the same patient at different time points. We introduced T345I SNP to mprF of the DAP-S MRSA strain using the gene exchange method with pIMAY vector. Further, we investigated the phenotype of the mutant strain, including drug susceptibility, cell surface positive charge, and growth speed. The mutant strain exhibited (i) resistance to DAP, (ii) up-regulation of positive surface charge, (iii) slower growth speed, and (iv) thickened cell walls. Hence, the SNP in mprF may have caused an up-regulation in MprF function, with a subsequent increase in positive surface charge. Cumulatively, these results demonstrated that the T345I amino acid substitution in mprF represents one of the primary causes of DAP-NS in MRSA strains. Public Library of Science 2021-01-22 /pmc/articles/PMC7822245/ /pubmed/33481910 http://dx.doi.org/10.1371/journal.pone.0245732 Text en © 2021 Nakamura et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Nakamura, Masaki
Kawada, Hayato
Uchida, Hiroki
Takagi, Yusuke
Obata, Shuichi
Eda, Ryotaro
Hanaki, Hideaki
Kitasato, Hidero
Single nucleotide polymorphism leads to daptomycin resistance causing amino acid substitution—T345I in MprF of clinically isolated MRSA strains
title Single nucleotide polymorphism leads to daptomycin resistance causing amino acid substitution—T345I in MprF of clinically isolated MRSA strains
title_full Single nucleotide polymorphism leads to daptomycin resistance causing amino acid substitution—T345I in MprF of clinically isolated MRSA strains
title_fullStr Single nucleotide polymorphism leads to daptomycin resistance causing amino acid substitution—T345I in MprF of clinically isolated MRSA strains
title_full_unstemmed Single nucleotide polymorphism leads to daptomycin resistance causing amino acid substitution—T345I in MprF of clinically isolated MRSA strains
title_short Single nucleotide polymorphism leads to daptomycin resistance causing amino acid substitution—T345I in MprF of clinically isolated MRSA strains
title_sort single nucleotide polymorphism leads to daptomycin resistance causing amino acid substitution—t345i in mprf of clinically isolated mrsa strains
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7822245/
https://www.ncbi.nlm.nih.gov/pubmed/33481910
http://dx.doi.org/10.1371/journal.pone.0245732
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