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New Phage-Derived Antibacterial Enzyme PolaR Targeting Rothia spp
Paulina Miernikiewicz1, Jakub Barylski2, Aleksandra Wilczak1
1Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wrocław, Poland.
Cells
|August 11, 2023
Summary
A novel endolysin, PolaR, targets and destroys Rothia bacteria, including in biofilms. This enzyme, derived from the gastric phageome, shows potential for treating Rothia infections without harming human cells.
Area of Science:
- Microbiology
- Bacteriophage therapy
- Bioinformatics
Background:
- Rothia species are opportunistic pathogens causing severe infections, especially in immunocompromised individuals.
- Rothia mucilaginosa promotes the growth of Pseudomonas aeruginosa, a significant ESKAPE pathogen.
- Endolysins are bacteriophage-derived enzymes with targeted antibacterial activity.
Purpose of the Study:
- To identify and characterize a novel endolysin targeting Rothia species.
- To investigate the potential of endolysins from the gastric mucosa phageome as therapeutic agents.
- To evaluate the safety and efficacy of the identified endolysin against Rothia bacteria.
Main Methods:
- Computational analysis of metagenomic sequencing data from human gastric mucosa phageomes.
- Expression, purification, and characterization of a candidate anti-Rothia endolysin (PolaR).
- Assessment of PolaR's activity against Rothia species, including biofilm-forming bacteria, and its cytotoxicity on mammalian cells.
Main Results:
- PolaR was identified as a specific endolysin targeting Rothia mucilaginosa and Rothia dentocariosa.
- PolaR effectively destroyed Rothia bacterial cells, including those in aggregated forms and biofilms.
- PolaR exhibited no cytotoxic or antiproliferative effects on mammalian cells.
Conclusions:
- PolaR is the first described endolysin with selective activity against Rothia species.
- PolaR demonstrates significant potential for combating Rothia infections, including those involving biofilms.
- The gastric mucosa phageome is a promising source for discovering novel antibacterial enzymes like PolaR.
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