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Inhibition of planktonic growth and biofilm formation of Staphylococcus aureus by entrectinib through disrupting the cell membrane

Over the last few decades, Staphylococcus aureus infection remain a major medical challenge and health concern worldwide. Biofilm formation and antibiotic resistance caused by S. aureus make it difficult to be eradicated from bacterial infections in clinics. In this study, our data demonstrated the...

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Autores principales: Liu, Shanghong, Xiong, Yanpeng, Xiao, Haitao, Zheng, Jinxin, Wen, Zewen, Li, Duoyun, Deng, Qiwen, Yu, Zhijian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9868760/
https://www.ncbi.nlm.nih.gov/pubmed/36699581
http://dx.doi.org/10.3389/fmicb.2022.1106319
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author Liu, Shanghong
Xiong, Yanpeng
Xiao, Haitao
Zheng, Jinxin
Wen, Zewen
Li, Duoyun
Deng, Qiwen
Yu, Zhijian
author_facet Liu, Shanghong
Xiong, Yanpeng
Xiao, Haitao
Zheng, Jinxin
Wen, Zewen
Li, Duoyun
Deng, Qiwen
Yu, Zhijian
author_sort Liu, Shanghong
collection PubMed
description Over the last few decades, Staphylococcus aureus infection remain a major medical challenge and health concern worldwide. Biofilm formation and antibiotic resistance caused by S. aureus make it difficult to be eradicated from bacterial infections in clinics. In this study, our data demonstrated the antibacterial and excellent anti-biofilm activity of entrectinib against S. aureus. Entrectinib also exhibited the good safety, suggesting no toxicity with antibacterial concentration of entrectinib toward the erythrocytes and mammalian 239 T cells. Moreover, entrectinib significantly reduced the bacterial burden of septic tissue in a murine model of MRSA infection. Global proteomic analysis of S. aureus treated with entrectinib showed significant changes in the expression levels of ribosomal structure-related (rpmC, rpmD, rplX, and rpsT) and oxidative stress-related proteins (Thioredoxin system), suggesting the possible inhibition of bacterial protein biosynthesis with entrectinib exposure. The increased production of reactive oxygen species (ROS) was demonstrated in the entrectinib-treated S. aureus, supported the impact of entrectinib on the expression changes of ROS-correlated proteins involved in oxidative stress. Furthermore, entrectinib-induced resistant S. aureus clone was selected by in vitro induction under entrectinib exposure and 3 amino acid mutations in the entrectinib-induced resistant S. aureus strain, 2 of which were located in the gene encoding Type II NADH: quinoneoxidoreductase and one were found in GTP pyrophosphokinase family protein. Finally, the bactericidal action of entrectinib on S. aureus were confirmed by disrupting the bacterial cell membrane. Conclusively, entrectinib exhibit the antibacterial and anti-biofilm activity by destroying cell membrane against S. aureus.
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spelling pubmed-98687602023-01-24 Inhibition of planktonic growth and biofilm formation of Staphylococcus aureus by entrectinib through disrupting the cell membrane Liu, Shanghong Xiong, Yanpeng Xiao, Haitao Zheng, Jinxin Wen, Zewen Li, Duoyun Deng, Qiwen Yu, Zhijian Front Microbiol Microbiology Over the last few decades, Staphylococcus aureus infection remain a major medical challenge and health concern worldwide. Biofilm formation and antibiotic resistance caused by S. aureus make it difficult to be eradicated from bacterial infections in clinics. In this study, our data demonstrated the antibacterial and excellent anti-biofilm activity of entrectinib against S. aureus. Entrectinib also exhibited the good safety, suggesting no toxicity with antibacterial concentration of entrectinib toward the erythrocytes and mammalian 239 T cells. Moreover, entrectinib significantly reduced the bacterial burden of septic tissue in a murine model of MRSA infection. Global proteomic analysis of S. aureus treated with entrectinib showed significant changes in the expression levels of ribosomal structure-related (rpmC, rpmD, rplX, and rpsT) and oxidative stress-related proteins (Thioredoxin system), suggesting the possible inhibition of bacterial protein biosynthesis with entrectinib exposure. The increased production of reactive oxygen species (ROS) was demonstrated in the entrectinib-treated S. aureus, supported the impact of entrectinib on the expression changes of ROS-correlated proteins involved in oxidative stress. Furthermore, entrectinib-induced resistant S. aureus clone was selected by in vitro induction under entrectinib exposure and 3 amino acid mutations in the entrectinib-induced resistant S. aureus strain, 2 of which were located in the gene encoding Type II NADH: quinoneoxidoreductase and one were found in GTP pyrophosphokinase family protein. Finally, the bactericidal action of entrectinib on S. aureus were confirmed by disrupting the bacterial cell membrane. Conclusively, entrectinib exhibit the antibacterial and anti-biofilm activity by destroying cell membrane against S. aureus. Frontiers Media S.A. 2023-01-09 /pmc/articles/PMC9868760/ /pubmed/36699581 http://dx.doi.org/10.3389/fmicb.2022.1106319 Text en Copyright © 2023 Liu, Xiong, Xiao, Zheng, Wen, Li, Deng and Yu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Liu, Shanghong
Xiong, Yanpeng
Xiao, Haitao
Zheng, Jinxin
Wen, Zewen
Li, Duoyun
Deng, Qiwen
Yu, Zhijian
Inhibition of planktonic growth and biofilm formation of Staphylococcus aureus by entrectinib through disrupting the cell membrane
title Inhibition of planktonic growth and biofilm formation of Staphylococcus aureus by entrectinib through disrupting the cell membrane
title_full Inhibition of planktonic growth and biofilm formation of Staphylococcus aureus by entrectinib through disrupting the cell membrane
title_fullStr Inhibition of planktonic growth and biofilm formation of Staphylococcus aureus by entrectinib through disrupting the cell membrane
title_full_unstemmed Inhibition of planktonic growth and biofilm formation of Staphylococcus aureus by entrectinib through disrupting the cell membrane
title_short Inhibition of planktonic growth and biofilm formation of Staphylococcus aureus by entrectinib through disrupting the cell membrane
title_sort inhibition of planktonic growth and biofilm formation of staphylococcus aureus by entrectinib through disrupting the cell membrane
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9868760/
https://www.ncbi.nlm.nih.gov/pubmed/36699581
http://dx.doi.org/10.3389/fmicb.2022.1106319
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