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Published on: September 11, 2020
The effectiveness of extended binding affinity of prophage lysin PlyARI against Streptococcus suis infection
Yuyi Xiao1,2,3, Rong Chen4, Min Li1,2,3
1OIE Reference Lab for Swine Streptococcosis, Nanjing, 210095, China.
Abstract:
Streptococcus suis is an important zoonotic pathogen. An increase in multi-drug-resistant strains has led to poor performance of traditional antibiotic therapies. Thus, alternative antibacterial agents are urgently needed. In this study, we identified a recombined and expressed lysin PlyARI derived from the novel serotype S. suis (Chz) prophage PhiARI0460-1. The recombinant PlyARI at a concentration of 10 µg/mL showed high bacteriolytic activity against 30 S. suis isolates. The minimum inhibitory concentration (MIC) of PlyARI against S. suis was found to be as low as 2 µg/mL, and the lytic efficiency could be maintained between the range of pH 4 and 12. Additionally, in a mouse infection model, a dose of 0.5 mg of PlyARI protected 10 out of 10 mice that were challenged with highly virulent S. suis strain HA9801. Furthermore, the binding specificity of PlyARI was evaluated by constructing a green fluorescent protein (GFP-ARIb), where GFP was fused with the PlyARI-SH3b (cell wall-binding domain, CBD), revealing a high affinity to S. suis, Staphylococcus aureus, and Streptococcus equi along with exhibiting a medium affinity to Streptococcus pneumoniae as well as Streptococcus agalactiae. Overall, our findings indicated that PlyARI may be an alternative antibacterial agent that was useful in treating and possibly the prevention of Streptococcal infections.
Insights
A novel lysin, PlyARI, shows potent antibacterial activity against drug-resistant Streptococcus suis. This potential new agent effectively killed S. suis in vitro and protected mice from infection, offering hope for new treatments.
Area of Science:
- Microbiology
- Bacteriology
- Antimicrobial Research
Background:
- Streptococcus suis is a significant zoonotic pathogen causing severe infections.
- Increasing multi-drug resistance in S. suis necessitates novel therapeutic strategies.
- Traditional antibiotics are becoming less effective against resistant strains.
Purpose of the Study:
- To identify and characterize a novel antibacterial agent against Streptococcus suis.
- To evaluate the efficacy and specificity of the lysin PlyARI.
- To explore PlyARI as a potential alternative to conventional antibiotics.
Main Methods:
- Recombinant expression and purification of lysin PlyARI from prophage PhiARI0460-1.
- In vitro assessment of bacteriolytic activity, minimum inhibitory concentration (MIC), and pH stability.
- In vivo efficacy testing using a mouse infection model.
- Evaluation of binding specificity using a green fluorescent protein (GFP) fusion protein.
Main Results:
- Recombinant PlyARI demonstrated high bacteriolytic activity against 30 S. suis isolates with an MIC of 2 µg/mL.
- PlyARI maintained lytic efficiency across a broad pH range (4-12).
- A dose of 0.5 mg PlyARI provided complete protection in a mouse model challenged with virulent S. suis.
- PlyARI exhibited high binding affinity for S. suis, Staphylococcus aureus, and Streptococcus equi.
Conclusions:
- PlyARI is a potent antibacterial agent effective against Streptococcus suis.
- Its broad pH stability and in vivo efficacy suggest therapeutic potential.
- PlyARI shows promise as an alternative antibacterial agent for treating and preventing Streptococcal infections.
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