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Published on: September 8, 2021
P-27/HP endolysin as antibacterial agent for antibiotic resistant Staphylococcus aureus of human infections
Ragini Gupta1, Yogendra Prasad
1Division of Biological Standardization, Indian Veterinary Research Institute, Izatnagar, 243122, Uttar Pradesh, India. ragini@iitk.ac.in
Abstract:
Staphylococcus aureus causes a wide range of suppurative infections in humans and animals. Due to its high virulence, ability to adopt various environmental conditions, and acquired multiple drug resistance, treatment of such infections has become difficult. Therefore, there is an immense need to develop alternate drug modalities to control this pathogen. In past few years, phage-encoded endolysin therapy has emerged as a new hope not only due to its ability to specifically kill the target bacteria irrespective of their antibiotic sensitivity but also because of minimum or no side effects, a problem associated with antibiotic therapy. In this article, we report purification of a broad spectrum anti-staphylococcal endolysin (P-27/HP endolysin) encoded by phage P-27/HP isolated from sewage water. On SDS-PAGE endolysin resolved in three polypeptides of molecular weights 33.5, 48.6, and 62.2 kDa. Endolysin exhibited maximum in vitro lytic activity at temperature between 35 and 40°C and pH 7.0. In vivo experiments revealed considerable (99.9%) elimination of S. aureus 27/HP from spleens of endolysin-treated mice and had saved them from death due to bacteremia caused by S. aureus 27/HP challenge infection. Thus, P-27/HP endolysin offers suitable substitute of antibiotics to control S. aureus infections.
Insights
Phage-encoded endolysins offer a promising alternative to antibiotics for treating Staphylococcus aureus infections. A novel P-27/HP endolysin effectively eliminated bacteria in mice, demonstrating its potential as a safe and effective therapeutic agent.
Area of Science:
- Microbiology
- Biotechnology
- Infectious Diseases
Background:
- Staphylococcus aureus infections are difficult to treat due to high virulence and antibiotic resistance.
- Antibiotic therapy for S. aureus infections can cause side effects.
- Phage-encoded endolysins are a potential alternative therapy with specific bacterial targeting and minimal side effects.
Purpose of the Study:
- To purify and characterize a novel broad-spectrum anti-staphylococcal endolysin (P-27/HP endolysin).
- To evaluate the efficacy of P-27/HP endolysin in controlling Staphylococcus aureus infections in a mouse model.
Main Methods:
- Purification of P-27/HP endolysin from phage P-27/HP.
- Analysis of endolysin purity and molecular weight using SDS-PAGE.
- Determination of optimal in vitro lytic activity conditions (temperature and pH).
- In vivo efficacy study in a mouse model of S. aureus bacteremia.
Main Results:
- Purified P-27/HP endolysin consists of three polypeptides (33.5, 48.6, and 62.2 kDa).
- Optimal lytic activity was observed at 35–40°C and pH 7.0.
- In vivo treatment resulted in 99.9% elimination of S. aureus from mouse spleens and survival from bacteremia.
Conclusions:
- P-27/HP endolysin is a potent anti-staphylococcal agent.
- This endolysin demonstrates significant efficacy in clearing S. aureus infections in vivo.
- P-27/HP endolysin presents a viable alternative to conventional antibiotics for managing S. aureus infections.
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