Novel Bacillus altitudinis endolysin (ArtE2) targeting both Gram-positive and Gram-negative bacteria

Abstract

Antibiotic resistance is a major global health concern. The development of new antibiotics and therapeutics is crucial for the future. Bacteriophages produce endolysins that induce bacterial lysis, making them a promising treatment option. Deep sequencing was used to identify and isolate genes encoding endolysins from Bacillus spp.. We characterized the biological activities of these endolysins. Additionally, this study focused on the design of a new chimeric endolysin, ArtE2, which combines endolysin-2 with a polycationic peptide to address the bacterial activity in gram-negative pathogenic bacteria. Using bioinformatic tools, we conducted three-dimensional modeling of the endolysin ArtE2 and its interactions with peptidoglycan fragments. In this study, we tested the activity of chimeric endolysins against both Gram-positive and Gram-negative bacteria. All endolysins share the same catalytic domain and diverse cell-binding domains. Some endolysins are highly specific to certain bacterial species or strains, whereas others have broader specificities. Histidine interactions are an important part of the mechanism by which ArtE2 connects with bacterial peptidoglycan. Additionally, the engineered endolysin ArtE2 was highly effective at killing Staphylococcus aureus and Escherichia coli. In silico analysis showed that the fusion did not negatively affect endolysin folding or activity. These findings suggest that ArtE2 could be used to develop efficient antibacterial controls targeting pathogenic Gram-positive and Gram-negative bacteria.