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New Insights Into the Antibacterial Mechanism of Cryptotanshinone, a Representative Diterpenoid Quinone From Salvia miltiorrhiza Bunge

The rapid rise of antibiotic resistance causes an urgent need for new antimicrobial agents with unique and different mechanisms of action. The respiratory chain is one such target involved in the redox balance and energy metabolism. As a natural quinone compound isolated from the root of Salvia milt...

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Autores principales: Chen, Bo-Chen, Ding, Zhi-Shan, Dai, Jian-Sheng, Chen, Ni-Pi, Gong, Xing-Wen, Ma, Lie-Feng, Qian, Chao-Dong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7950322/
https://www.ncbi.nlm.nih.gov/pubmed/33717044
http://dx.doi.org/10.3389/fmicb.2021.647289
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author Chen, Bo-Chen
Ding, Zhi-Shan
Dai, Jian-Sheng
Chen, Ni-Pi
Gong, Xing-Wen
Ma, Lie-Feng
Qian, Chao-Dong
author_facet Chen, Bo-Chen
Ding, Zhi-Shan
Dai, Jian-Sheng
Chen, Ni-Pi
Gong, Xing-Wen
Ma, Lie-Feng
Qian, Chao-Dong
author_sort Chen, Bo-Chen
collection PubMed
description The rapid rise of antibiotic resistance causes an urgent need for new antimicrobial agents with unique and different mechanisms of action. The respiratory chain is one such target involved in the redox balance and energy metabolism. As a natural quinone compound isolated from the root of Salvia miltiorrhiza Bunge, cryptotanshinone (CT) has been previously demonstrated against a wide range of Gram-positive bacteria including multidrug-resistant pathogens. Although superoxide radicals induced by CT are proposed to play an important role in the antibacterial effect of this agent, its mechanism of action is still unclear. In this study, we have shown that CT is a bacteriostatic agent rather than a bactericidal agent. Metabolome analysis suggested that CT might act as an antibacterial agent targeting the cell membrane. CT did not cause severe damage to the bacterial membrane but rapidly dissipated membrane potential, implying that this compound could be a respiratory chain inhibitor. Oxygen consumption analysis in staphylococcal membrane vesicles implied that CT acted as respiratory chain inhibitor probably by targeting type II NADH:quinone dehydrogenase (NDH-2). Molecular docking study suggested that the compound would competitively inhibit the binding of quinone to NDH-2. Consistent with the hypothesis, the antimicrobial activity of CT was blocked by menaquinone, and the combination of CT with thioridazine but not 2-n-heptyl-4-hydroxyquinoline-N-oxide exerted synergistic activity against Staphylococcus aureus. Additionally, combinations of CT with other inhibitors targeting different components of the bacterial respiratory chain exhibit potent synergistic activities against S. aureus, suggesting a promising role in combination therapies.
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spelling pubmed-79503222021-03-12 New Insights Into the Antibacterial Mechanism of Cryptotanshinone, a Representative Diterpenoid Quinone From Salvia miltiorrhiza Bunge Chen, Bo-Chen Ding, Zhi-Shan Dai, Jian-Sheng Chen, Ni-Pi Gong, Xing-Wen Ma, Lie-Feng Qian, Chao-Dong Front Microbiol Microbiology The rapid rise of antibiotic resistance causes an urgent need for new antimicrobial agents with unique and different mechanisms of action. The respiratory chain is one such target involved in the redox balance and energy metabolism. As a natural quinone compound isolated from the root of Salvia miltiorrhiza Bunge, cryptotanshinone (CT) has been previously demonstrated against a wide range of Gram-positive bacteria including multidrug-resistant pathogens. Although superoxide radicals induced by CT are proposed to play an important role in the antibacterial effect of this agent, its mechanism of action is still unclear. In this study, we have shown that CT is a bacteriostatic agent rather than a bactericidal agent. Metabolome analysis suggested that CT might act as an antibacterial agent targeting the cell membrane. CT did not cause severe damage to the bacterial membrane but rapidly dissipated membrane potential, implying that this compound could be a respiratory chain inhibitor. Oxygen consumption analysis in staphylococcal membrane vesicles implied that CT acted as respiratory chain inhibitor probably by targeting type II NADH:quinone dehydrogenase (NDH-2). Molecular docking study suggested that the compound would competitively inhibit the binding of quinone to NDH-2. Consistent with the hypothesis, the antimicrobial activity of CT was blocked by menaquinone, and the combination of CT with thioridazine but not 2-n-heptyl-4-hydroxyquinoline-N-oxide exerted synergistic activity against Staphylococcus aureus. Additionally, combinations of CT with other inhibitors targeting different components of the bacterial respiratory chain exhibit potent synergistic activities against S. aureus, suggesting a promising role in combination therapies. Frontiers Media S.A. 2021-02-25 /pmc/articles/PMC7950322/ /pubmed/33717044 http://dx.doi.org/10.3389/fmicb.2021.647289 Text en Copyright © 2021 Chen, Ding, Dai, Chen, Gong, Ma and Qian. http://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
Chen, Bo-Chen
Ding, Zhi-Shan
Dai, Jian-Sheng
Chen, Ni-Pi
Gong, Xing-Wen
Ma, Lie-Feng
Qian, Chao-Dong
New Insights Into the Antibacterial Mechanism of Cryptotanshinone, a Representative Diterpenoid Quinone From Salvia miltiorrhiza Bunge
title New Insights Into the Antibacterial Mechanism of Cryptotanshinone, a Representative Diterpenoid Quinone From Salvia miltiorrhiza Bunge
title_full New Insights Into the Antibacterial Mechanism of Cryptotanshinone, a Representative Diterpenoid Quinone From Salvia miltiorrhiza Bunge
title_fullStr New Insights Into the Antibacterial Mechanism of Cryptotanshinone, a Representative Diterpenoid Quinone From Salvia miltiorrhiza Bunge
title_full_unstemmed New Insights Into the Antibacterial Mechanism of Cryptotanshinone, a Representative Diterpenoid Quinone From Salvia miltiorrhiza Bunge
title_short New Insights Into the Antibacterial Mechanism of Cryptotanshinone, a Representative Diterpenoid Quinone From Salvia miltiorrhiza Bunge
title_sort new insights into the antibacterial mechanism of cryptotanshinone, a representative diterpenoid quinone from salvia miltiorrhiza bunge
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7950322/
https://www.ncbi.nlm.nih.gov/pubmed/33717044
http://dx.doi.org/10.3389/fmicb.2021.647289
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