{"doi":"10.1073/pnas.0500268102","title":"Expression of an additional cathelicidin antimicrobial peptide protects against bacterial skin infection","abstract":"<jats:p>\n                    Cathelicidin antimicrobial peptides are effectors of innate immune defense in mammals. Humans and mice have only one cathelicidin gene, whereas domesticated mammals such as the pig, cow, and horse have multiple cathelicidin genes. We hypothesized that the evolution of multiple cathelicidin genes provides these animals with enhanced resistance to infection. To test this, we investigated the effects of the addition of cathelicidins by combining synthetic cathelicidin peptides\n                    <jats:italic>in vitro</jats:italic>\n                    , by producing human keratinocytes that overexpress cathelicidins in culture, or by producing transgenic mice that constitutively overexpress cathelicidins\n                    <jats:italic>in vivo</jats:italic>\n                    . The porcine cathelicidin peptide PR-39 acted additively with human cathelicidin LL-37 to kill group A\n                    <jats:italic>Streptococcus</jats:italic>\n                    (GAS). Lentiviral delivery of PR-39 enhanced killing of GAS by human keratinocytes. Finally, transgenic mice expressing PR-39 under the influence of a K14 promoter showed increased resistance to GAS skin infection (50% smaller necrotic ulcers and 60% fewer surviving bacteria). Similarly constructed transgenic mice designed to overexpress their native cathelicidin did not show increased resistance. These findings demonstrate that targeted gene transfer of a xenobiotic cathelicidin confers resistance against infection and suggests the benefit of duplication and divergence in the evolution of antimicrobial peptides.\n                  </jats:p>","journal":"Proceedings of the National Academy of Sciences","year":2005,"id":604943,"datarank":5.91490315327746,"base_score":4.897839799950911,"endowment":4.897839799950911,"self_citation_contribution":0.7346759699926367,"citation_network_contribution":5.180227183284823,"self_endowment_contribution":0.7346759699926367,"citer_contribution":5.180227183284823,"corpus_percentile":null,"corpus_rank":null,"citation_count":133,"citer_count":117,"citers_with_citation_signal":108,"citers_with_endowment":108,"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":1552254,"name":"Takaaki Ohtake","orcid":null,"position":1,"is_corresponding":false},{"id":1552255,"name":"Mohamed Zaiou","orcid":null,"position":2,"is_corresponding":false},{"id":1552256,"name":"Masamoto Murakami","orcid":null,"position":3,"is_corresponding":false},{"id":1552257,"name":"Jennifer A. Rudisill","orcid":null,"position":4,"is_corresponding":false},{"id":1552258,"name":"Kenneth H. Lin","orcid":null,"position":5,"is_corresponding":false},{"id":249754,"name":"Richard L. Gallo","orcid":"0000-0002-1401-7861","position":6,"is_corresponding":false},{"id":1552253,"name":"Phillip H. A. Lee","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Expression of an additional cathelicidin antimicrobial peptide protects against bacterial skin infection","abstract":"<jats:p>\n                    Cathelicidin antimicrobial peptides are effectors of innate immune defense in mammals. Humans and mice have only one cathelicidin gene, whereas domesticated mammals such as the pig, cow, and horse have multiple cathelicidin genes. We hypothesized that the evolution of multiple cathelicidin genes provides these animals with enhanced resistance to infection. To test this, we investigated the effects of the addition of cathelicidins by combining synthetic cathelicidin peptides\n                    <jats:italic>in vitro</jats:italic>\n                    , by producing human keratinocytes that overexpress cathelicidins in culture, or by producing transgenic mice that constitutively overexpress cathelicidins\n                    <jats:italic>in vivo</jats:italic>\n                    . The porcine cathelicidin peptide PR-39 acted additively with human cathelicidin LL-37 to kill group A\n                    <jats:italic>Streptococcus</jats:italic>\n                    (GAS). Lentiviral delivery of PR-39 enhanced killing of GAS by human keratinocytes. Finally, transgenic mice expressing PR-39 under the influence of a K14 promoter showed increased resistance to GAS skin infection (50% smaller necrotic ulcers and 60% fewer surviving bacteria). Similarly constructed transgenic mice designed to overexpress their native cathelicidin did not show increased resistance. These findings demonstrate that targeted gene transfer of a xenobiotic cathelicidin confers resistance against infection and suggests the benefit of duplication and divergence in the evolution of antimicrobial peptides.\n                  </jats:p>","is_dataset_classified":null,"base_score":4.897839799950911,"endowment":4.897839799950911,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"15728389","pmcid":"PMC549293","openalex_id":"https://openalex.org/W1611178069","authors":[],"funders":[{"funder_name":"NCI NIH HHS","grant_id":"1T32 CA 81211","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"AI 052453","title":null},{"funder_name":"NIAMS NIH HHS","grant_id":"R01 AR045676","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"R37 AI052453","title":null},{"funder_name":"NIAMS NIH HHS","grant_id":"AR 45676","title":null},{"funder_name":"NCI NIH HHS","grant_id":"T32 CA081211","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"R01 AI052453","title":null}],"total_grants":7,"fwci":8.1245,"citation_percentile":0.98154613,"influential_citations":0,"citation_trend":[{"year":2012,"count":8},{"year":2013,"count":9},{"year":2014,"count":5},{"year":2015,"count":5},{"year":2016,"count":5},{"year":2017,"count":4},{"year":2018,"count":5},{"year":2019,"count":4},{"year":2020,"count":4},{"year":2021,"count":5},{"year":2022,"count":5},{"year":2023,"count":2},{"year":2024,"count":4},{"year":2025,"count":2},{"year":2026,"count":1}],"oa_status":"bronze","license":null,"oa_locations":[{"url":"https://www.pnas.org/content/pnas/102/10/3750.full.pdf","host_type":"journal"},{"url":"https://www.pnas.org/content/pnas/102/10/3750.full.pdf","host_type":"publisher"},{"url":"https://pnas.org/doi/pdf/10.1073/pnas.0500268102","host_type":"publisher"},{"url":"https://doi.org/10.1073/pnas.0500268102","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/15728389","host_type":"repository"},{"url":"https://hal.science/hal-04335434","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/549293","host_type":"repository"}],"fields_of_study":["Antimicrobial Peptides and Activities","Biochemical and Structural Characterization","Transgenic Plants and Applications","Animals","Antimicrobial Cationic Peptides","Humans","Keratinocytes","Mice","Mice, Transgenic","Skin Diseases, Bacterial","Streptococcal Infections","Streptococcus pyogenes","Swine","Cathelicidins"],"mesh_terms":["Animals","Humans","Mice, Transgenic","Streptococcal Infections","Streptococcus pyogenes","Swine","Keratinocytes","Skin Diseases, Bacterial","Antimicrobial Cationic Peptides","Mice","Cathelicidins"],"keywords":["Cathelicidin","Antimicrobial peptides","Biology","Microbiology","Innate immune system","Antimicrobial","Immune system","Immunology"],"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":"2026-07-30T01:15:06.260854Z","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":[]}