Repurposing auranofin combined with colistin to effectively combat fish-pathogenic Edwardsiella piscicida
Edwardsiella piscicida (E. piscicida) is an important opportunistic fish pathogen, and infects various species of cultured fish posing a great challenge to the aquaculture industry globally. To address the frequent emergence of multi-antibiotics resistant E. piscicida and the shortage of effective a...
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Elsevier
2025-07-01
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| Series: | Aquaculture Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352513425002169 |
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| author | Jinfang Lu Yangbin Shi Yajing Pan Hans-Peter Grossart Luyu Mei Danli Xie Wanchun Guan He Zhang Yongliang Lou |
| author_facet | Jinfang Lu Yangbin Shi Yajing Pan Hans-Peter Grossart Luyu Mei Danli Xie Wanchun Guan He Zhang Yongliang Lou |
| author_sort | Jinfang Lu |
| collection | DOAJ |
| description | Edwardsiella piscicida (E. piscicida) is an important opportunistic fish pathogen, and infects various species of cultured fish posing a great challenge to the aquaculture industry globally. To address the frequent emergence of multi-antibiotics resistant E. piscicida and the shortage of effective antimicrobial treatments, this study aimed to develop a novel combination therapy against E. piscicida. The combination of the FDA approved drug auranofin (originally used to treat rheumatoid arthritis) with colistin exerted great bactericidal effects against E. piscicida both in vitro and in vivo. Auranofin disrupted the thioredoxin system, and decreased the minimum inhibitory concentration (MICcolistin) of E. piscicida. Further, auranofin combined with colistin significantly inhibited the growth of E. piscicida isolates, even resulting in cell death. A mechanistic study revealed that the combination remarkably damaged the bacterial membrane increasing its permeability, and it also promoted a decrease of membrane potential, thereby exacerbating oxidative stress and the bactericidal effects of colistin. Importantly, auranofin combined with colistin strongly attenuated the essential bacterial two-component system, lipopolysaccharide modification, motility and virulence pathways. Moreover, the combination of both chemicals also efficiently reduced E. piscicida burden in the gill, intestine and head kidney of infected zebrafish (Danio rerio), and significantly improved their survival rate. Overall, these results suggested that the thioredoxin-mediated redox cascade is a potential target for novel antimicrobials, and that auranofin combined with colistin could be repurposed to effectively combat Edwardsiella infections. |
| format | Article |
| id | doaj-art-b37544e2562c45d9b0ca10a62e18de0b |
| institution | DOAJ |
| issn | 2352-5134 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Aquaculture Reports |
| spelling | doaj-art-b37544e2562c45d9b0ca10a62e18de0b2025-08-20T03:09:51ZengElsevierAquaculture Reports2352-51342025-07-014210283010.1016/j.aqrep.2025.102830Repurposing auranofin combined with colistin to effectively combat fish-pathogenic Edwardsiella piscicidaJinfang Lu0Yangbin Shi1Yajing Pan2Hans-Peter Grossart3Luyu Mei4Danli Xie5Wanchun Guan6He Zhang7Yongliang Lou8Wenzhou Key Laboratory of Sanitary Microbiology, Key Laboratory of Laboratory Medicine, Ministry of Education, China, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, ChinaWenzhou Key Laboratory of Sanitary Microbiology, Key Laboratory of Laboratory Medicine, Ministry of Education, China, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, ChinaWenzhou Key Laboratory of Sanitary Microbiology, Key Laboratory of Laboratory Medicine, Ministry of Education, China, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, ChinaUniversity of Potsdam, Institute of Biochemistry and Biology, Potsdam 14469, Germany; Leibniz-Institute of Freshwater Ecology and Inland Fisheries (IGB), Stechlin 16775, GermanyWenzhou Key Laboratory of Sanitary Microbiology, Key Laboratory of Laboratory Medicine, Ministry of Education, China, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, ChinaWenzhou Key Laboratory of Sanitary Microbiology, Key Laboratory of Laboratory Medicine, Ministry of Education, China, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, ChinaWenzhou Key Laboratory of Sanitary Microbiology, Key Laboratory of Laboratory Medicine, Ministry of Education, China, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, ChinaZhejiang Provincial Key Laboratory for Subtropical Water Environment and Marine Biological Resources Protection, National and Local Joint Engineering Research Center of Ecological Treatment Technology for Urban Water Pollution, College of Life and Environmental Sciences, Wenzhou University, Wenzhou, Zhejiang 325035, China; Corresponding authors.Wenzhou Key Laboratory of Sanitary Microbiology, Key Laboratory of Laboratory Medicine, Ministry of Education, China, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China; Corresponding authors.Edwardsiella piscicida (E. piscicida) is an important opportunistic fish pathogen, and infects various species of cultured fish posing a great challenge to the aquaculture industry globally. To address the frequent emergence of multi-antibiotics resistant E. piscicida and the shortage of effective antimicrobial treatments, this study aimed to develop a novel combination therapy against E. piscicida. The combination of the FDA approved drug auranofin (originally used to treat rheumatoid arthritis) with colistin exerted great bactericidal effects against E. piscicida both in vitro and in vivo. Auranofin disrupted the thioredoxin system, and decreased the minimum inhibitory concentration (MICcolistin) of E. piscicida. Further, auranofin combined with colistin significantly inhibited the growth of E. piscicida isolates, even resulting in cell death. A mechanistic study revealed that the combination remarkably damaged the bacterial membrane increasing its permeability, and it also promoted a decrease of membrane potential, thereby exacerbating oxidative stress and the bactericidal effects of colistin. Importantly, auranofin combined with colistin strongly attenuated the essential bacterial two-component system, lipopolysaccharide modification, motility and virulence pathways. Moreover, the combination of both chemicals also efficiently reduced E. piscicida burden in the gill, intestine and head kidney of infected zebrafish (Danio rerio), and significantly improved their survival rate. Overall, these results suggested that the thioredoxin-mediated redox cascade is a potential target for novel antimicrobials, and that auranofin combined with colistin could be repurposed to effectively combat Edwardsiella infections.http://www.sciencedirect.com/science/article/pii/S2352513425002169Edwardsiella piscicidaAntibiotic resistanceAuranofinThioredoxin reductaseCombination therapy |
| spellingShingle | Jinfang Lu Yangbin Shi Yajing Pan Hans-Peter Grossart Luyu Mei Danli Xie Wanchun Guan He Zhang Yongliang Lou Repurposing auranofin combined with colistin to effectively combat fish-pathogenic Edwardsiella piscicida Aquaculture Reports Edwardsiella piscicida Antibiotic resistance Auranofin Thioredoxin reductase Combination therapy |
| title | Repurposing auranofin combined with colistin to effectively combat fish-pathogenic Edwardsiella piscicida |
| title_full | Repurposing auranofin combined with colistin to effectively combat fish-pathogenic Edwardsiella piscicida |
| title_fullStr | Repurposing auranofin combined with colistin to effectively combat fish-pathogenic Edwardsiella piscicida |
| title_full_unstemmed | Repurposing auranofin combined with colistin to effectively combat fish-pathogenic Edwardsiella piscicida |
| title_short | Repurposing auranofin combined with colistin to effectively combat fish-pathogenic Edwardsiella piscicida |
| title_sort | repurposing auranofin combined with colistin to effectively combat fish pathogenic edwardsiella piscicida |
| topic | Edwardsiella piscicida Antibiotic resistance Auranofin Thioredoxin reductase Combination therapy |
| url | http://www.sciencedirect.com/science/article/pii/S2352513425002169 |
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