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- Title
Fraxetin Targeting to Sortase A Decreases the Pathogenicity of Streptococcus agalactiae to Nile Tilapia.
- Authors
Dong, Jing; Zhang, Yuze; Yang, Qiuhong; Liu, Yongtao; Zhou, Shun; Ai, Xiaohui
- Abstract
Simple Summary: Tilapia is the second-most-farmed fish worldwide which plays a critical role in providing high-quality proteins to human. However, infections caused by S. agalactiae result in huge economic losses. Moreover, the spreads of antibiotic resistance restrict the use of antibiotics in treating S. agalactiae infections. Here, we tried to develop anti-S. agalactiae drugs by inhibiting SrtA to overcome infections caused by resistant bacterial strains. Sortase A (SrtA) is responsible for anchoring surface proteins to the cell wall, and has been identified as a promising target developing anti-infective drugs of Gram-positive bacteria. The aim of the study was to identify inhibitors of Streptococcus agalactiae (S. agalactiae) SrtA from natural compounds to overcome the spread of antibiotic resistance in aquaculture. Here, we found that the MIC of fraxetin against S. agalactiae was higher than 256 μg/mL, indicating that fraxetin had no anti- S. agalactiae activity. But fraxetin could dose-dependently decrease the activity of SrtA in vitro at concentrations ranging between 4–32 μg/mL by a fluorescence resonance energy transfer (FRET) assay. Moreover, the inhibition of SrtA by fraxetin decreased the anchoring of surface proteins with the LPXTG motif to the cell wall by detecting the immunofluorescence change of serine-rich repeat protein 1 (Srr1) on the bacterial cell surface. The results of fibronectin binding and cell adhesion assays indicated that fraxetin could significantly decrease the adhesion ability of S. agalactiae in a dose-dependent manner. The results were further proven by immunofluorescence staining. Animal challenge results showed that treatment with fraxetin could reduce the mortality of tilapia infected with S. agalactiae to 46.67%, indicating that fraxetin could provide a significant amount of protection to tilapia by inactivating SrtA. Taken together, these findings provided a novel inhibitor of S. agalactiae SrtA and a promising candidate for treating S. agalactiae infections in aquaculture.
- Subjects
NILE tilapia; STREPTOCOCCUS agalactiae; FLUORESCENCE resonance energy transfer; BACTERIAL cell surfaces
- Publication
Animals (2076-2615), 2024, Vol 14, Issue 9, p1337
- ISSN
2076-2615
- Publication type
Article
- DOI
10.3390/ani14091337