{"doi":"10.1111/1751-7915.70237","title":"Antibacterial Activity of a Fused Endolysin <scp>ENDO</scp> ‐1252/ <scp>KL9P</scp> Against Multiple Serovars of <i>Salmonella enterica</i>","abstract":"Salmonella enterica (SE) is one of the most prevalent enteric pathogens globally and infects humans through contaminated food and water sources. The rising trend of antibiotic-resistant SE strains poses a critical threat to public health. Bacteriophage-encoded endolysins evolve a promising alternative as antimicrobial agents for combating SE infections. These enzymes target the peptidoglycan layer of bacterial cells, causing cell lysis and death. However, the use of endolysins against Gram-negative bacteria is challenging due to the composition of the outer membrane, which acts as a barrier preventing the endolysins from reaching the peptidoglycan layer. KL9P is a short amphipathic peptide containing both hydrophobic and hydrophilic regions, enabling it to interact with membranes and aqueous environments. In this study, an endolysin ENDO-1252, a Salmonella bacteriophage-encoded enzyme, was fused with a short peptide KL9P and produced an advanced endolysin, ENDO-1252/KL9P, which enhanced its ability to lyse multiple serovars of SE. ENDO-1252/KL9P exhibited potent lytic activity against SE strains with optimal bactericidal effects observed at 20 μM and incubation at 37°C in 20 mM HEPES buffer (pH 7.4). The lytic activity of this endolysin was also evaluated under various conditions, including pH ranges and temperatures, revealing that ENDO-1252/KL9P retained significant lytic activity across a range of temperatures (25°C-40°C) and pH values (6.0-9.0). The fusion protein demonstrated the highest lytic efficiency against SE serovars, specifically S. Enteritidis, S. Heidelberg, and S. Pullorum. Immunofluorescence analysis confirmed the binding of ENDO-1252/KL9P to the bacterial cell wall, indicating the co-localization with the peptidoglycan layer. These results suggest that ENDO-1252/KL9P is a promising antibacterial agent inhibiting predominant serovars of SE, showing enhanced lytic activity without outer membrane permeabilizers.","journal":"Microbial Biotechnology","year":2025,"id":534974,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9554,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1418117,"name":"Kanchan Thapa","orcid":"0000-0002-2698-3506","position":1,"is_corresponding":false},{"id":662167,"name":"Anna Phan","orcid":"0000-0001-8133-9513","position":2,"is_corresponding":false},{"id":293767,"name":"Aditi Mohapatra","orcid":null,"position":3,"is_corresponding":false},{"id":1418594,"name":"Muhammad Hashmi","orcid":null,"position":4,"is_corresponding":false},{"id":1418595,"name":"Kayla Bleich","orcid":null,"position":5,"is_corresponding":false},{"id":470837,"name":"Debabrata Biswas","orcid":null,"position":6,"is_corresponding":false},{"id":1418116,"name":"Chuan‐Wei Tung","orcid":"0000-0003-3850-4813","position":0,"is_corresponding":true}],"reference_count":52,"raw_metadata":null,"created_at":"2026-07-19T02:51:52.019261Z","pmid":"41063560","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}