Guanosine enhances the bactericidal effect of ceftiofur sodium on Streptococcus suis by activating bacterial metabolism
The emergence and rapid development of antibiotic resistance poses a serious threat to global public health. Streptococcus suis (S. suis) is an important zoonotic pathogen, and the development of its antibiotic resistance has made the infections difficult to treat. The combination of non-antibiotic...
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Taylor & Francis Group
2025-12-01
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Series: | Virulence |
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Online Access: | https://www.tandfonline.com/doi/10.1080/21505594.2025.2453525 |
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author | Yue Dong Xiaona Liu Shanshan Xiong Mingyu Cao Haojie Wu Long Chen Mengmeng Zhao Yadan Zheng Zhiyun Zhang Yanyan Liu Yanhua Li Qianwei Qu Chunliu Dong |
author_facet | Yue Dong Xiaona Liu Shanshan Xiong Mingyu Cao Haojie Wu Long Chen Mengmeng Zhao Yadan Zheng Zhiyun Zhang Yanyan Liu Yanhua Li Qianwei Qu Chunliu Dong |
author_sort | Yue Dong |
collection | DOAJ |
description | The emergence and rapid development of antibiotic resistance poses a serious threat to global public health. Streptococcus suis (S. suis) is an important zoonotic pathogen, and the development of its antibiotic resistance has made the infections difficult to treat. The combination of non-antibiotic compounds with antibiotics is considered a promising strategy against multidrug-resistant bacteria. However, the mechanism by which metabolites act as antibiotic adjuvant remains unclear. Here, we found that guanosine metabolism was repressed in multidrug-resistant S. suis. Exogenous guanosine promoted the antibacterial effects of ceftiofur sodium (CEF) in vitro and in vivo. Furthermore, we demonstrated that exogenous guanosine promoted the biosynthesis of purine pathway, TCA cycle and bacterial respiration, which make bacteria more sensitive to the killing effect of antibacterial. In addition, the function of the cell membrane is affected by guanosine and the accumulation of antimicrobials in the bacteria increased. Bacterial-oxidative stress and DNA damage induced by guanosine is also one of the mechanisms by which the antibacterial effect is enhanced. These results suggest that guanosine is a promising adjuvant for antibacterial drugs and provide new theoretical basis for the clinical treatment of S. suis infection. |
format | Article |
id | doaj-art-bb508ec0dad34af891f6088966c60097 |
institution | Kabale University |
issn | 2150-5594 2150-5608 |
language | English |
publishDate | 2025-12-01 |
publisher | Taylor & Francis Group |
record_format | Article |
series | Virulence |
spelling | doaj-art-bb508ec0dad34af891f6088966c600972025-02-07T05:43:14ZengTaylor & Francis GroupVirulence2150-55942150-56082025-12-0116110.1080/21505594.2025.2453525Guanosine enhances the bactericidal effect of ceftiofur sodium on Streptococcus suis by activating bacterial metabolismYue Dong0Xiaona Liu1Shanshan Xiong2Mingyu Cao3Haojie Wu4Long Chen5Mengmeng Zhao6Yadan Zheng7Zhiyun Zhang8Yanyan Liu9Yanhua Li10Qianwei Qu11Chunliu Dong12College of Veterinary Medicine, Northeast Agricultural University, Harbin, Heilongjiang, ChinaCollege of Veterinary Medicine, Northeast Agricultural University, Harbin, Heilongjiang, ChinaCollege of Veterinary Medicine, Northeast Agricultural University, Harbin, Heilongjiang, ChinaCollege of Veterinary Medicine, Northeast Agricultural University, Harbin, Heilongjiang, ChinaCollege of Veterinary Medicine, Northeast Agricultural University, Harbin, Heilongjiang, ChinaCollege of Veterinary Medicine, Northeast Agricultural University, Harbin, Heilongjiang, ChinaCollege of Veterinary Medicine, Northeast Agricultural University, Harbin, Heilongjiang, ChinaCollege of Veterinary Medicine, Northeast Agricultural University, Harbin, Heilongjiang, ChinaCollege of Veterinary Medicine, Northeast Agricultural University, Harbin, Heilongjiang, ChinaCollege of Veterinary Medicine, Northeast Agricultural University, Harbin, Heilongjiang, ChinaCollege of Veterinary Medicine, Northeast Agricultural University, Harbin, Heilongjiang, ChinaCollege of Veterinary Medicine, Northeast Agricultural University, Harbin, Heilongjiang, ChinaCollege of Veterinary Medicine, Northeast Agricultural University, Harbin, Heilongjiang, ChinaThe emergence and rapid development of antibiotic resistance poses a serious threat to global public health. Streptococcus suis (S. suis) is an important zoonotic pathogen, and the development of its antibiotic resistance has made the infections difficult to treat. The combination of non-antibiotic compounds with antibiotics is considered a promising strategy against multidrug-resistant bacteria. However, the mechanism by which metabolites act as antibiotic adjuvant remains unclear. Here, we found that guanosine metabolism was repressed in multidrug-resistant S. suis. Exogenous guanosine promoted the antibacterial effects of ceftiofur sodium (CEF) in vitro and in vivo. Furthermore, we demonstrated that exogenous guanosine promoted the biosynthesis of purine pathway, TCA cycle and bacterial respiration, which make bacteria more sensitive to the killing effect of antibacterial. In addition, the function of the cell membrane is affected by guanosine and the accumulation of antimicrobials in the bacteria increased. Bacterial-oxidative stress and DNA damage induced by guanosine is also one of the mechanisms by which the antibacterial effect is enhanced. These results suggest that guanosine is a promising adjuvant for antibacterial drugs and provide new theoretical basis for the clinical treatment of S. suis infection.https://www.tandfonline.com/doi/10.1080/21505594.2025.2453525Antibiotic adjuvantbacterial resistanceStreptococcus suisguanosineceftiofur sodium |
spellingShingle | Yue Dong Xiaona Liu Shanshan Xiong Mingyu Cao Haojie Wu Long Chen Mengmeng Zhao Yadan Zheng Zhiyun Zhang Yanyan Liu Yanhua Li Qianwei Qu Chunliu Dong Guanosine enhances the bactericidal effect of ceftiofur sodium on Streptococcus suis by activating bacterial metabolism Virulence Antibiotic adjuvant bacterial resistance Streptococcus suis guanosine ceftiofur sodium |
title | Guanosine enhances the bactericidal effect of ceftiofur sodium on Streptococcus suis by activating bacterial metabolism |
title_full | Guanosine enhances the bactericidal effect of ceftiofur sodium on Streptococcus suis by activating bacterial metabolism |
title_fullStr | Guanosine enhances the bactericidal effect of ceftiofur sodium on Streptococcus suis by activating bacterial metabolism |
title_full_unstemmed | Guanosine enhances the bactericidal effect of ceftiofur sodium on Streptococcus suis by activating bacterial metabolism |
title_short | Guanosine enhances the bactericidal effect of ceftiofur sodium on Streptococcus suis by activating bacterial metabolism |
title_sort | guanosine enhances the bactericidal effect of ceftiofur sodium on streptococcus suis by activating bacterial metabolism |
topic | Antibiotic adjuvant bacterial resistance Streptococcus suis guanosine ceftiofur sodium |
url | https://www.tandfonline.com/doi/10.1080/21505594.2025.2453525 |
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