A novel lysin Ply1228 provides efficient protection against Streptococcus suis type 2 infection in a murine
Zijing Wang1, Xiao Liu1, Zhaoxin Shi1
1State Key Laboratory for Zoonotic Diseases, Key Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun 130062, PR China.
Abstract:
Streptococcus suis is an important zoonotic pathogen that is difficult to control with antibiotics due to the widespread development of multidrug-resistant strains. Phage lysin is considered a potential therapeutic agent to combat S. suis. In this study, the novel lysin Ply1228 derived from the prophage of S. suis type 12 was identified. Bioinformatics analysis showed that Ply1228 contains a CHAP catalytic domain, which is a binding domain composed of a CW-7 binding motif and an amidase-2 catalytic domain. The CHAP catalytic domain is essential for the bactericidal function of lysin Ply1228 and does not depend on the presence of Ca2+. C34 and H99 of the CHAP domain were identified as the key active sites. The CW-7 binding motif plays a key binding role in Ply1228. Ply1228 can specifically lyse S. suis, including types 2, 3, 7, 9, 10, 12, 14, and 27. Within 10 min, Ply1228 killed 4 log of the S. suis population, which had a starting concentration of approximately 107 CFU/mL. In addition, Ply1228 showed favourable thermal and pH stability. The therapeutic effect of Ply1228 was further investigated in a mouse model of S. suis bacteremia. The administration of the lysin Ply1228 (200 μg/mouse) 1 h after the intraperitoneal injection of 2 × MLD of SS2 strain SC225 was sufficient to protect the mice (P < 0.0001) and significantly reduced the bacterial loads in the blood and organs (livers, spleens, lungs and kidneys). The levels of inflammation and histopathological damage in infected mice were effectively relieved after the Ply1228 treatment. These results indicate that Ply1228 might represent a new enzybiotic candidate for S. suis infection.
Insights
A novel phage lysin, Ply1228, effectively targets multidrug-resistant Streptococcus suis. This enzybiotic shows potent bactericidal activity and therapeutic benefits in a mouse model, offering a promising alternative to antibiotics.
Area of Science:
- Microbiology
- Biotechnology
- Infectious Diseases
Background:
- Streptococcus suis is a significant zoonotic pathogen with increasing antibiotic resistance.
- Phage lysins are emerging as potential therapeutic agents against bacterial infections.
Purpose of the Study:
- To identify and characterize a novel phage lysin, Ply1228, for combating Streptococcus suis infections.
- To evaluate the efficacy of Ply1228 as a therapeutic agent against S. suis.
Main Methods:
- Bioinformatics analysis of the Ply1228 lysin structure and function.
- In vitro bactericidal assays against S. suis strains.
- In vivo therapeutic efficacy study in a mouse model of S. suis bacteremia.
Main Results:
- Ply1228 possesses a CHAP catalytic domain and a CW-7 binding motif, essential for its bactericidal activity.
- Ply1228 demonstrated rapid and specific lysis of multiple S. suis serotypes in vitro.
- In vivo, Ply1228 treatment significantly reduced bacterial load, protected mice from mortality, and alleviated inflammation and tissue damage.
Conclusions:
- Ply1228 is a potent enzybiotic with broad-spectrum activity against S. suis.
- Ply1228 exhibits favorable stability and therapeutic potential for treating S. suis infections.
- This novel lysin represents a promising alternative to conventional antibiotics for S. suis control.
