ArticleMicrobiology spectrum2022
On the Occurrence and Multimerization of Two-Polypeptide Phage Endolysins Encoded in Single Genes.
Article in Microbiology spectrum, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 10 citations in OpenAlex.
- PhaLP 2.0: extending the community-oriented phage lysin database with a SUBLYME pipeline for metagenomic discovery.Database : the journal of biological databases and curation · 2026Article
- Heterodimerization of staphylococcal phage φ2638A endolysin isoforms and their functional role in bacterial lysis.microLife · 2025Article
- Bacteriophage-derived endolysins as innovative antimicrobials against bovine mastitis-causing streptococci and staphylococci: a state-of-the-art review.Acta veterinaria Scandinavica · 2024Review
- Engineering strategies and challenges of endolysin as an antibacterial agent against Gram-negative bacteria.Microbial biotechnology · 2024Review
- Understanding the Molecular Basis for Homodimer Formation of the Pneumococcal Endolysin Cpl-1.ACS infectious diseases · 2023Article
- Cell wall modifications that alter the exolytic activity of lactococcal phage endolysins have little impact on phage growth.Frontiers in microbiology · 2023Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Bacteriophages (phages) and other viruses are extremely efficient in packing their genetic information, with several described cases of overlapping genes encoded in different open reading frames (ORFs). While less frequently reported, specific cases exist in which two overlapping ORFs are in frame and share the stop codon. Here, we studied the occurrence of this genetic arrangement in endolysins, the phage enzymes that cut the bacterial cell wall peptidoglycan to release the virion progeny. After screening over 3,000 endolysin sequences of phages infecting Gram-positive bacteria, we found evidence that this coding strategy is frequent in endolysin genes. Our bioinformatics predictions were experimentally validated by demonstrating that two polypeptides are indeed produced from these genes. Additionally, we show that in some cases the two polypeptides need to interact and multimerize to generate the active endolysin. By studying in detail one selected example, we uncovered a heteromeric endolysin with a 1:5 subunit stoichiometry that has never been described before. Hence, we conclude that the occurrence of endolysin genes encoding two polypeptide isoforms by in-frame overlapping ORFs, as well as their organization as enzymatic complexes, appears more common than previously thought, therefore challenging the established view of endolysins being mostly formed by single, monomeric polypeptide chains.
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