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...

Full description

Saved in:
Bibliographic Details
Main Authors: 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
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:Virulence
Subjects:
Online Access:https://www.tandfonline.com/doi/10.1080/21505594.2025.2453525
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1825206818333261824
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
work_keys_str_mv AT yuedong guanosineenhancesthebactericidaleffectofceftiofursodiumonstreptococcussuisbyactivatingbacterialmetabolism
AT xiaonaliu guanosineenhancesthebactericidaleffectofceftiofursodiumonstreptococcussuisbyactivatingbacterialmetabolism
AT shanshanxiong guanosineenhancesthebactericidaleffectofceftiofursodiumonstreptococcussuisbyactivatingbacterialmetabolism
AT mingyucao guanosineenhancesthebactericidaleffectofceftiofursodiumonstreptococcussuisbyactivatingbacterialmetabolism
AT haojiewu guanosineenhancesthebactericidaleffectofceftiofursodiumonstreptococcussuisbyactivatingbacterialmetabolism
AT longchen guanosineenhancesthebactericidaleffectofceftiofursodiumonstreptococcussuisbyactivatingbacterialmetabolism
AT mengmengzhao guanosineenhancesthebactericidaleffectofceftiofursodiumonstreptococcussuisbyactivatingbacterialmetabolism
AT yadanzheng guanosineenhancesthebactericidaleffectofceftiofursodiumonstreptococcussuisbyactivatingbacterialmetabolism
AT zhiyunzhang guanosineenhancesthebactericidaleffectofceftiofursodiumonstreptococcussuisbyactivatingbacterialmetabolism
AT yanyanliu guanosineenhancesthebactericidaleffectofceftiofursodiumonstreptococcussuisbyactivatingbacterialmetabolism
AT yanhuali guanosineenhancesthebactericidaleffectofceftiofursodiumonstreptococcussuisbyactivatingbacterialmetabolism
AT qianweiqu guanosineenhancesthebactericidaleffectofceftiofursodiumonstreptococcussuisbyactivatingbacterialmetabolism
AT chunliudong guanosineenhancesthebactericidaleffectofceftiofursodiumonstreptococcussuisbyactivatingbacterialmetabolism