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抗生素对药物诱导的抑菌细胞的杀伤作用。

Antibiotic killing of drug-induced bacteriostatic cells.

作者信息

Gil-Gil Teresa, Berryhill Brandon A

机构信息

Department of Biology, Emory University; Atlanta, Georgia, 30322, USA.

Program in Microbiology and Molecular Genetics, Graduate Division of Biological and Biomedical Sciences, Laney Graduate School, Emory University; Atlanta, GA, 30322, USA.

出版信息

bioRxiv. 2024 Sep 6:2024.09.06.611640. doi: 10.1101/2024.09.06.611640.

DOI:10.1101/2024.09.06.611640
PMID:39282318
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11398456/
Abstract

BACKGROUND

There is a long-standing belief that bacteriostatic drugs are inherently antagonistic to the action of bactericidal antibiotics. This belief is primarily due to the fact that the action of most bactericidal antibiotics requires the target bacteria to be growing. Since bacteriostatic drugs stop the growth of treated bacteria, these drugs would necessarily work against one another. We have recently shown that bacteria treated with high concentrations of bacteriostatic drugs retain some metabolic activity, dividing on average once per day.

OBJECTIVES

We seek to determine if this low level of growth is sufficient to allow for bactericidal antibiotics of different classes to still kill after bacteria are treated with bacteriostatic drugs.

METHODS

We first treated and with two different bacteriostatic drugs, followed by one of three bactericidal drugs of three different classes. The density of these bacteria was tracked over six days to determine the amount of killing that occurred.

RESULTS

Our results question this long-standing belief by demonstrating conditions where sequential treatment with a bacteriostatic then bactericidal antibiotic is as or more effective than treatment with a bactericidal drug alone.

CONCLUSIONS

These results raise the need to investigate the pharmacodynamics of the joint action of bacteriostatic and bactericidal antibiotics and .

摘要

背景

长期以来,人们一直认为抑菌药物本质上与杀菌抗生素的作用相互拮抗。这种观点主要源于大多数杀菌抗生素的作用需要靶细菌处于生长状态这一事实。由于抑菌药物会阻止被治疗细菌的生长,所以这些药物必然会相互拮抗。我们最近发现,用高浓度抑菌药物处理过的细菌仍保留一些代谢活性,平均每天分裂一次。

目的

我们试图确定这种低水平的生长是否足以使不同类别的杀菌抗生素在细菌经抑菌药物处理后仍能发挥杀菌作用。

方法

我们先用两种不同的抑菌药物处理[具体细菌名称未给出]和[具体细菌名称未给出],然后再用三种不同类别的三种杀菌药物中的一种进行处理。在六天内跟踪这些细菌的密度,以确定发生的杀菌量。

结果

我们的结果对这一长期存在的观点提出了质疑,结果表明,先使用抑菌药物然后再使用杀菌抗生素的序贯治疗,与单独使用杀菌药物相比,效果相同或更好。

结论

这些结果表明有必要研究抑菌抗生素和杀菌抗生素联合作用的药效学。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adb4/11398456/6baf4f186c25/nihpp-2024.09.06.611640v1-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adb4/11398456/be3ce6fc2f05/nihpp-2024.09.06.611640v1-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adb4/11398456/6baf4f186c25/nihpp-2024.09.06.611640v1-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adb4/11398456/be3ce6fc2f05/nihpp-2024.09.06.611640v1-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adb4/11398456/6baf4f186c25/nihpp-2024.09.06.611640v1-f0002.jpg

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本文引用的文献

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Nat Commun. 2024 Sep 11;15(1):7936. doi: 10.1038/s41467-024-52166-z.
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Unraveling resistance mechanisms in combination therapy: A comprehensive review of recent advances and future directions.解析联合治疗中的耐药机制:近期进展与未来方向的全面综述
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The transmutation of Escherichia coli ATCC 25922 to small colony variants (SCVs) E. coli strain as a result of exposure to gentamicin.
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What's the Matter with MICs: Bacterial Nutrition, Limiting Resources, and Antibiotic Pharmacodynamics.MIC 怎么了:细菌营养、限制资源和抗生素药效动力学。
Microbiol Spectr. 2023 Jun 15;11(3):e0409122. doi: 10.1128/spectrum.04091-22. Epub 2023 May 3.
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Mechanisms and therapeutic potential of collateral sensitivity to antibiotics.抗生素 collateral 敏感性的机制及治疗潜力
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