{"doi":"10.1128/aac.48.10.3817-3822.2004","title":"Therapy of Experimental\n            <i>Pseudomonas</i>\n            Infections with a Nonreplicating Genetically Modified Phage","abstract":"<jats:title>ABSTRACT</jats:title>\n          <jats:p>\n            Bacteriophage therapy of bacterial infections has received renewed attention owing to the increasing prevalence of antibiotic-resistant pathogens. A side effect of many antibiotics as well as of phage therapy with lytic phage is the release of cell wall components, e.g., endotoxins of gram-negative bacteria, which mediate the general pathological aspects of septicemia. Here we explored an alternative strategy by using genetically engineered nonreplicating, nonlytic phage to combat an experimental\n            <jats:italic>Pseudomonas aeruginosa</jats:italic>\n            infection. An export protein gene of the\n            <jats:italic>P. aeruginosa</jats:italic>\n            filamentous phage Pf3 was replaced with a restriction endonuclease gene. This rendered the Pf3 variant (Pf3R) nonreplicative and concomitantly prevented the release of the therapeutic agent from the target cell. The Pf3R phage efficiently killed a wild-type host in vitro, while endotoxin release was kept to a minimum. Treatment of\n            <jats:italic>P. aeruginosa</jats:italic>\n            infections of mice with Pf3R or with a replicating lytic phage resulted in comparable survival rates upon challenge with a minimal lethal dose of 3. However, the survival rate after phage therapy with Pf3R was significantly higher than that with the lytic phage upon challenge with a minimal lethal dose of 5. This higher survival rate correlated with a reduced inflammatory response elicited by Pf3R treatment relative to that with the lytic phage. Therefore, this study suggests that the increased survival rate of Pf3R-treated mice could result from reduced endotoxin release. Thus, the use of a nonreplicating modified phage for the delivery of genes encoding proteins toxic to bacterial pathogens may open up a new avenue in antimicrobial therapy.\n          </jats:p>","journal":"Antimicrobial Agents and Chemotherapy","year":2004,"id":642400,"datarank":0.7846662925281881,"base_score":5.231108616854587,"endowment":5.231108616854587,"self_citation_contribution":0.7846662925281881,"citation_network_contribution":0.0,"self_endowment_contribution":0.7846662925281881,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":186,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1670901,"name":"André Habel","orcid":null,"position":1,"is_corresponding":false},{"id":1670902,"name":"Uwe von Ahsen","orcid":null,"position":2,"is_corresponding":false},{"id":1670903,"name":"Alexander von Gabain","orcid":null,"position":3,"is_corresponding":false},{"id":1670904,"name":"Udo Bläsi","orcid":null,"position":4,"is_corresponding":false},{"id":1670900,"name":"Steven Hagens","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Therapy of Experimental\n            <i>Pseudomonas</i>\n            Infections with a Nonreplicating Genetically Modified Phage","abstract":"<jats:title>ABSTRACT</jats:title>\n          <jats:p>\n            Bacteriophage therapy of bacterial infections has received renewed attention owing to the increasing prevalence of antibiotic-resistant pathogens. A side effect of many antibiotics as well as of phage therapy with lytic phage is the release of cell wall components, e.g., endotoxins of gram-negative bacteria, which mediate the general pathological aspects of septicemia. Here we explored an alternative strategy by using genetically engineered nonreplicating, nonlytic phage to combat an experimental\n            <jats:italic>Pseudomonas aeruginosa</jats:italic>\n            infection. An export protein gene of the\n            <jats:italic>P. aeruginosa</jats:italic>\n            filamentous phage Pf3 was replaced with a restriction endonuclease gene. This rendered the Pf3 variant (Pf3R) nonreplicative and concomitantly prevented the release of the therapeutic agent from the target cell. The Pf3R phage efficiently killed a wild-type host in vitro, while endotoxin release was kept to a minimum. Treatment of\n            <jats:italic>P. aeruginosa</jats:italic>\n            infections of mice with Pf3R or with a replicating lytic phage resulted in comparable survival rates upon challenge with a minimal lethal dose of 3. However, the survival rate after phage therapy with Pf3R was significantly higher than that with the lytic phage upon challenge with a minimal lethal dose of 5. This higher survival rate correlated with a reduced inflammatory response elicited by Pf3R treatment relative to that with the lytic phage. Therefore, this study suggests that the increased survival rate of Pf3R-treated mice could result from reduced endotoxin release. Thus, the use of a nonreplicating modified phage for the delivery of genes encoding proteins toxic to bacterial pathogens may open up a new avenue in antimicrobial therapy.\n          </jats:p>","is_dataset_classified":null,"base_score":5.231108616854587,"endowment":5.231108616854587,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"15388440","pmcid":"PMC521880","openalex_id":"https://openalex.org/W2163204395","authors":[],"funders":[],"total_grants":0,"fwci":5.3406,"citation_percentile":0.95643462,"influential_citations":0,"citation_trend":[{"year":2012,"count":12},{"year":2013,"count":9},{"year":2014,"count":16},{"year":2015,"count":10},{"year":2016,"count":10},{"year":2017,"count":14},{"year":2018,"count":11},{"year":2019,"count":13},{"year":2020,"count":10},{"year":2021,"count":7},{"year":2022,"count":4},{"year":2023,"count":10},{"year":2024,"count":5},{"year":2025,"count":7},{"year":2026,"count":3}],"oa_status":"green","license":"https://journals.asm.org/non-commercial-tdm-license","oa_locations":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/521880","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/521880","host_type":"repository"},{"url":"https://journals.asm.org/doi/pdf/10.1128/AAC.48.10.3817-3822.2004","host_type":"publisher"},{"url":"https://doi.org/10.1128/aac.48.10.3817-3822.2004","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/15388440","host_type":"repository"},{"url":"http://europepmc.org/pmc/articles/PMC521880","host_type":"repository"}],"fields_of_study":["Bacteriophages and microbial interactions","Vibrio bacteria research studies","Viral gastroenteritis research and epidemiology","Animals","Bacteriophage Pf1","Endotoxins","Interleukin-6","Mice","Mice, Inbred BALB C","Organisms, Genetically Modified","Plasmids","Pseudomonas Infections","Pseudomonas aeruginosa","Tumor Necrosis Factor-alpha","Virus Replication"],"mesh_terms":["Animals","Endotoxins","Mice, Inbred BALB C","Plasmids","Pseudomonas aeruginosa","Pseudomonas Infections","Tumor Necrosis Factor-alpha","Virus Replication","Interleukin-6","Bacteriophage Pf1","Organisms, Genetically Modified","Mice"],"keywords":["Lytic cycle","Phage therapy","Microbiology","Bacteriophage","Pseudomonas aeruginosa","Biology","Antibiotics","Bacteria","Multidrug tolerance","Virology","Escherichia coli","Gene","Virus","Genetics","Biofilm"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-07T22:38:36.793861Z","pmid":null,"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":[]}