Andrographolide reverses the susceptibility of Streptococcus suis to aminoglycoside antibiotics by proton motive force
Abstract Background The global rise in multidrug-resistant bacteria has significantly undermined the efficacy of traditional antibiotics. Multidrug-resistant Streptococcus suis (S. suis), a pathogen capable of infecting pigs and humans, has been identified as a critical threat, causing severe mening...
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BMC
2025-02-01
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| Series: | BMC Veterinary Research |
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| Online Access: | https://doi.org/10.1186/s12917-024-04430-z |
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| author | Bingqian Xue Hailong Li ShuJi Gao Yingying Quan Yuxin Wang Li Yi Yang Wang |
| author_facet | Bingqian Xue Hailong Li ShuJi Gao Yingying Quan Yuxin Wang Li Yi Yang Wang |
| author_sort | Bingqian Xue |
| collection | DOAJ |
| description | Abstract Background The global rise in multidrug-resistant bacteria has significantly undermined the efficacy of traditional antibiotics. Multidrug-resistant Streptococcus suis (S. suis), a pathogen capable of infecting pigs and humans, has been identified as a critical threat, causing severe meningitis and rapid mortality. In response, researchers have increasingly focused on herbal compounds as non-traditional antimicrobial agents, which can inhibit bacterial growth while minimizing the risk of resistance development. This study investigates the mechanism through which andrographolide (AP) restores the susceptibility of S. suis to aminoglycoside antibiotics. Methods The intracellular ΔpH in S. suis was assessed using the 2’,7’ -bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein (BCCF-AM) probe to evaluate alterations in the proton motive force (PMF) following treatment with AP. Non-targeted metabolomics was employed to confirm changes in the metabolic profile of S. suis upon exposure to AP. Finally, an in vivo infection model was utilized to evaluate the therapeutic efficacy of AP in combination with antibiotics. Results Extensive in vitro experiments demonstrated that AP significantly enhances the activity of aminoglycoside antibiotics against diverse pathogens, including S. suis. Further studies revealed that bacterial death results from AP-mediated upregulation of the S. suis PMF, which enhances cellular uptake of tobramycin (TOB). Moreover, AP significantly upregulated pyruvate metabolism in S. suis, accelerated the tricarboxylic acid (TCA) cycle, and increased nicotinamide adenine dinucleotide (NADH) production. This metabolic shift further augmented the PMF. Combining AP with aminoglycoside antibiotics significantly reduced bacterial load and organ lesions in various organs in mice. Conclusion AP holds promise as an adjuvant to aminoglycoside antibiotics for combating S. suis-induced infections, offering a theoretical foundation for clinical applications. |
| format | Article |
| id | doaj-art-73faca26f86a49f7917f7d91c48a470d |
| institution | DOAJ |
| issn | 1746-6148 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Veterinary Research |
| spelling | doaj-art-73faca26f86a49f7917f7d91c48a470d2025-08-20T02:48:27ZengBMCBMC Veterinary Research1746-61482025-02-0121111310.1186/s12917-024-04430-zAndrographolide reverses the susceptibility of Streptococcus suis to aminoglycoside antibiotics by proton motive forceBingqian Xue0Hailong Li1ShuJi Gao2Yingying Quan3Yuxin Wang4Li Yi5Yang Wang6College of Animal Science and Technology, Henan University of Science and TechnologyCollege of Animal Science and Technology, Henan University of Science and TechnologyCollege of Animal Science and Technology, Henan University of Science and TechnologyCollege of Animal Science and Technology, Henan University of Science and TechnologyCollege of Animal Science and Technology, Henan University of Science and TechnologyHenan Provincial Engineering Research Center for Detection and Prevention and Control of Emerging Infectious Diseases in Livestock and PoultryCollege of Animal Science and Technology, Henan University of Science and TechnologyAbstract Background The global rise in multidrug-resistant bacteria has significantly undermined the efficacy of traditional antibiotics. Multidrug-resistant Streptococcus suis (S. suis), a pathogen capable of infecting pigs and humans, has been identified as a critical threat, causing severe meningitis and rapid mortality. In response, researchers have increasingly focused on herbal compounds as non-traditional antimicrobial agents, which can inhibit bacterial growth while minimizing the risk of resistance development. This study investigates the mechanism through which andrographolide (AP) restores the susceptibility of S. suis to aminoglycoside antibiotics. Methods The intracellular ΔpH in S. suis was assessed using the 2’,7’ -bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein (BCCF-AM) probe to evaluate alterations in the proton motive force (PMF) following treatment with AP. Non-targeted metabolomics was employed to confirm changes in the metabolic profile of S. suis upon exposure to AP. Finally, an in vivo infection model was utilized to evaluate the therapeutic efficacy of AP in combination with antibiotics. Results Extensive in vitro experiments demonstrated that AP significantly enhances the activity of aminoglycoside antibiotics against diverse pathogens, including S. suis. Further studies revealed that bacterial death results from AP-mediated upregulation of the S. suis PMF, which enhances cellular uptake of tobramycin (TOB). Moreover, AP significantly upregulated pyruvate metabolism in S. suis, accelerated the tricarboxylic acid (TCA) cycle, and increased nicotinamide adenine dinucleotide (NADH) production. This metabolic shift further augmented the PMF. Combining AP with aminoglycoside antibiotics significantly reduced bacterial load and organ lesions in various organs in mice. Conclusion AP holds promise as an adjuvant to aminoglycoside antibiotics for combating S. suis-induced infections, offering a theoretical foundation for clinical applications.https://doi.org/10.1186/s12917-024-04430-zStreptococcus suisAminoglycoside antibioticsPMFAdjuvant |
| spellingShingle | Bingqian Xue Hailong Li ShuJi Gao Yingying Quan Yuxin Wang Li Yi Yang Wang Andrographolide reverses the susceptibility of Streptococcus suis to aminoglycoside antibiotics by proton motive force BMC Veterinary Research Streptococcus suis Aminoglycoside antibiotics PMF Adjuvant |
| title | Andrographolide reverses the susceptibility of Streptococcus suis to aminoglycoside antibiotics by proton motive force |
| title_full | Andrographolide reverses the susceptibility of Streptococcus suis to aminoglycoside antibiotics by proton motive force |
| title_fullStr | Andrographolide reverses the susceptibility of Streptococcus suis to aminoglycoside antibiotics by proton motive force |
| title_full_unstemmed | Andrographolide reverses the susceptibility of Streptococcus suis to aminoglycoside antibiotics by proton motive force |
| title_short | Andrographolide reverses the susceptibility of Streptococcus suis to aminoglycoside antibiotics by proton motive force |
| title_sort | andrographolide reverses the susceptibility of streptococcus suis to aminoglycoside antibiotics by proton motive force |
| topic | Streptococcus suis Aminoglycoside antibiotics PMF Adjuvant |
| url | https://doi.org/10.1186/s12917-024-04430-z |
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