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Thymine Sensitizes Gram-Negative Pathogens to Antibiotic Killing
Diminished antibiotic susceptibility of bacterial pathogens is an increasingly serious threat to human and animal health. Alternative strategies are required to combat antibiotic refractory bacteria. Bacterial metabolic state has been shown to play a critical role in its susceptibility to antibiotic...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7875874/ https://www.ncbi.nlm.nih.gov/pubmed/33584625 http://dx.doi.org/10.3389/fmicb.2021.622798 |
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author | Liu, Yuan Yang, Kangni Jia, Yuqian Shi, Jingru Tong, Ziwen Wang, Zhiqiang |
author_facet | Liu, Yuan Yang, Kangni Jia, Yuqian Shi, Jingru Tong, Ziwen Wang, Zhiqiang |
author_sort | Liu, Yuan |
collection | PubMed |
description | Diminished antibiotic susceptibility of bacterial pathogens is an increasingly serious threat to human and animal health. Alternative strategies are required to combat antibiotic refractory bacteria. Bacterial metabolic state has been shown to play a critical role in its susceptibility to antibiotic killing. However, the adjuvant potential of nucleotides in combination with antibiotics to kill Gram-negative pathogens remains unknown. Herein, we found that thymine potentiated ciprofloxacin killing against both sensitive and resistant-E. coli in a growth phase-independent manner. Similar promotion effects were also observed for other bactericidal antibiotics, including ampicillin and kanamycin, in the fight against four kinds of Gram-negative bacteria. The mechanisms underlying this finding were that exogenous thymine could upregulate bacterial metabolism including increased TCA cycle and respiration, which thereby promote the production of ATP and ROS. Subsequently, metabolically inactive bacteria were converted to active bacteria and restored its susceptibility to antibiotic killing. In Galleria mellonella infection model, thymine effectively improved ciprofloxacin activity against E. coli. Taken together, our results demonstrated that thymine potentiates bactericidal antibiotics activity against Gram-negative pathogens through activating bacterial metabolism, providing a universal strategy to overcome Gram-negative pathogens. |
format | Online Article Text |
id | pubmed-7875874 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-78758742021-02-12 Thymine Sensitizes Gram-Negative Pathogens to Antibiotic Killing Liu, Yuan Yang, Kangni Jia, Yuqian Shi, Jingru Tong, Ziwen Wang, Zhiqiang Front Microbiol Microbiology Diminished antibiotic susceptibility of bacterial pathogens is an increasingly serious threat to human and animal health. Alternative strategies are required to combat antibiotic refractory bacteria. Bacterial metabolic state has been shown to play a critical role in its susceptibility to antibiotic killing. However, the adjuvant potential of nucleotides in combination with antibiotics to kill Gram-negative pathogens remains unknown. Herein, we found that thymine potentiated ciprofloxacin killing against both sensitive and resistant-E. coli in a growth phase-independent manner. Similar promotion effects were also observed for other bactericidal antibiotics, including ampicillin and kanamycin, in the fight against four kinds of Gram-negative bacteria. The mechanisms underlying this finding were that exogenous thymine could upregulate bacterial metabolism including increased TCA cycle and respiration, which thereby promote the production of ATP and ROS. Subsequently, metabolically inactive bacteria were converted to active bacteria and restored its susceptibility to antibiotic killing. In Galleria mellonella infection model, thymine effectively improved ciprofloxacin activity against E. coli. Taken together, our results demonstrated that thymine potentiates bactericidal antibiotics activity against Gram-negative pathogens through activating bacterial metabolism, providing a universal strategy to overcome Gram-negative pathogens. Frontiers Media S.A. 2021-01-28 /pmc/articles/PMC7875874/ /pubmed/33584625 http://dx.doi.org/10.3389/fmicb.2021.622798 Text en Copyright © 2021 Liu, Yang, Jia, Shi, Tong and Wang. 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 Liu, Yuan Yang, Kangni Jia, Yuqian Shi, Jingru Tong, Ziwen Wang, Zhiqiang Thymine Sensitizes Gram-Negative Pathogens to Antibiotic Killing |
title | Thymine Sensitizes Gram-Negative Pathogens to Antibiotic Killing |
title_full | Thymine Sensitizes Gram-Negative Pathogens to Antibiotic Killing |
title_fullStr | Thymine Sensitizes Gram-Negative Pathogens to Antibiotic Killing |
title_full_unstemmed | Thymine Sensitizes Gram-Negative Pathogens to Antibiotic Killing |
title_short | Thymine Sensitizes Gram-Negative Pathogens to Antibiotic Killing |
title_sort | thymine sensitizes gram-negative pathogens to antibiotic killing |
topic | Microbiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7875874/ https://www.ncbi.nlm.nih.gov/pubmed/33584625 http://dx.doi.org/10.3389/fmicb.2021.622798 |
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