{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:24:48Z","timestamp":1760059488093,"version":"build-2065373602"},"reference-count":33,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T00:00:00Z","timestamp":1750377600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31900328","ZR2023MH345"],"award-info":[{"award-number":["31900328","ZR2023MH345"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["31900328","ZR2023MH345"],"award-info":[{"award-number":["31900328","ZR2023MH345"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Regulating the innate immune response against infections, particularly drug-resistant bacteria, is a key focus in anti-infection therapy. Cathelicidins, found in vertebrates, are crucial for pathogen resistance. Few studies have explored gecko cathelicidins\u2019 anti-infection properties. Recently, five new cathelicidins (Gj-CATH1-5) were identified in Gekko japonicus. The peptide Gj-CATH5, from G. japonicus, shows promise against Pseudomonas aeruginosa through various mechanisms. This study examined Gj-CATH5\u2019s protective effects using in vitro and in vivo models, finding that it significantly reduced bacterial load in a mouse infection model when administered before or shortly after infection. Flow cytometry and the plate counting method showed that Gj-CATH5 boosts neutrophil and macrophage activity, enhancing chemotaxis, phagocytosis, and bactericidal functions. Gj-CATH5 increases ROS production, MPO activity, and NET formation, aiding pathogen clearance. Its amphipathic \u03b1-helical structure supports broad-spectrum bactericidal activity (MBC: 4\u20138 \u03bcg\/mL) against Gram-negative and antibiotic-resistant bacteria. Gj-CATH5 is minimally cytotoxic (&lt;8% hemolysis at 200 \u03bcg\/mL) and preserves cell viability at therapeutic levels. These results highlight Gj-CATH5\u2019s dual role in pathogen elimination and immune modulation, offering a promising approach to combat multidrug-resistant infections while reducing inflammation. This study enhances the understanding of reptilian cathelicidins and lays the groundwork for peptide-based immune therapies against difficult bacterial infections.<\/jats:p>","DOI":"10.3390\/biom15070908","type":"journal-article","created":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T05:17:42Z","timestamp":1750396662000},"page":"908","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploring the Antimicrobial and Immunomodulatory Potential of Gecko-Derived Cathelicidin Gj-CATH5"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7659-6897","authenticated-orcid":false,"given":"Shasha","family":"Cai","sequence":"first","affiliation":[{"name":"The Key Laboratory for Medical Functional Nanomaterials, College of Medical Engineering, Jining Medical University, Jining 272067, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ningyang","family":"Gao","sequence":"additional","affiliation":[{"name":"The Key Laboratory for Medical Functional Nanomaterials, College of Medical Engineering, Jining Medical University, Jining 272067, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junhan","family":"Wang","sequence":"additional","affiliation":[{"name":"The Key Laboratory for Medical Functional Nanomaterials, College of Medical Engineering, Jining Medical University, Jining 272067, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Li","sequence":"additional","affiliation":[{"name":"The Key Laboratory for Medical Functional Nanomaterials, College of Medical Engineering, Jining Medical University, Jining 272067, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1038\/nrmicro2745","article-title":"Modulating immunity as a therapy for bacterial infections","volume":"10","author":"Hancock","year":"2012","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e47","DOI":"10.1016\/S1473-3099(16)00078-5","article-title":"Host-directed therapies for infectious diseases: Current status, recent progress, and future prospects","volume":"16","author":"Zumla","year":"2016","journal-title":"Lancet Infect. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"613","DOI":"10.2174\/1568026616666160713143017","article-title":"Models of In-Vivo Bacterial Infections for the Development of Antimicrobial Peptide-based Drugs","volume":"17","author":"Brunetti","year":"2017","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1038\/nri.2016.29","article-title":"The immunology of host defence peptides: Beyond antimicrobial activity","volume":"16","author":"Hancock","year":"2016","journal-title":"Nat. Rev. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1016\/j.imbio.2010.07.003","article-title":"Host defense peptides and their antimicrobial-immunomodulatory duality","volume":"216","author":"Steinstraesser","year":"2011","journal-title":"Immunobiology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1038\/nchembio.1393","article-title":"Immune modulation by multifaceted cationic host defense (antimicrobial) peptides","volume":"9","author":"Hilchie","year":"2013","journal-title":"Nat. Chem. Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1159\/000336630","article-title":"Cationic host defence peptides: Multifaceted role in immune modulation and inflammation","volume":"4","author":"Choi","year":"2012","journal-title":"J. Innate Immun."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2075","DOI":"10.1021\/acs.jmedchem.8b00036","article-title":"Python Cathelicidin CATHPb1 Protects against Multidrug-Resistant Staphylococcal Infections by Antimicrobial-Immunomodulatory Duality","volume":"61","author":"Cai","year":"2018","journal-title":"J. Med. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3309","DOI":"10.1128\/AAC.06304-11","article-title":"Efficacy of OH-CATH30 and its analogs against drug-resistant bacteria in vitro and in mouse models","volume":"56","author":"Li","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1080\/11250003.2013.783632","article-title":"Bioinformatic and molecular characterization of cathelicidin-like peptides isolated from the green lizard Anolis carolinensis (Reptilia: Lepidosauria: Iguanidae)","volume":"80","author":"Benato","year":"2013","journal-title":"Ital. J. Zool."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Cai, S., Meng, K., Liu, P., Cao, X., and Wang, G. (2021). Suppressive effects of gecko cathelicidin on biofilm formation and cariogenic virulence factors of Streptococcus mutans. Arch. Oral. Biol., 129.","DOI":"10.1016\/j.archoralbio.2021.105205"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"173649","DOI":"10.1016\/j.ejphar.2020.173649","article-title":"Derivatives of gecko cathelicidin-related antioxidant peptide facilitate skin wound healing","volume":"890","author":"Cai","year":"2021","journal-title":"Eur. J. Pharmacol."},{"key":"ref_13","first-page":"1690","article-title":"Anti-Pseudomonas aeruginosa IgY antibodies promote bacterial opsonization and augment the phagocytic activity of polymorphonuclear neutrophils","volume":"12","author":"Thomsen","year":"2016","journal-title":"Hum. Vaccines Immunother."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1619","DOI":"10.1073\/pnas.1108464109","article-title":"Toll-like receptor 5 (TLR5), IL-1\u03b2 secretion, and asparagine endopeptidase are critical factors for alveolar macrophage phagocytosis and bacterial killing\u2014Toll-like receptor 5 (TLR5), IL-1\u03b2 secretion, and asparagine endopeptidase are critical factors","volume":"109","author":"Descamps","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1038\/cdd.2014.169","article-title":"The generation of neutrophils in the bone marrow is controlled by autophagy","volume":"22","author":"Yousefi","year":"2015","journal-title":"Cell Death Differ."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Jurado-Mart\u00edn, I., Sainz-Mej\u00edas, M., and McClean, S. (2021). Pseudomonas aeruginosa: An Audacious Pathogen with an Adaptable Arsenal of Virulence Factors. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22063128"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"eabd6197","DOI":"10.1126\/sciimmunol.abd6197","article-title":"Longitudinal immune profiling reveals key myeloid signatures associated with COVID-19","volume":"5","author":"Mann","year":"2020","journal-title":"Sci. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Liu, C., Shan, B., Qi, J., and Ma, Y. (2017). Systemic Responses of Multidrug-Resistant Pseudomonas aeruginosa and Acinetobacter baumannii Following Exposure to the Antimicrobial Peptide Cathelicidin-BF Imply Multiple Intracellular Targets. Front. Cell Infect. Microbiol., 7.","DOI":"10.3389\/fcimb.2017.00466"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"McHugh, B.J., Wang, R., Li, H.N., Beaumont, P.E., Kells, R., Stevens, H., Young, L., Rossi, A.G., Gray, R.D., and Dorin, J.R. (2019). Cathelicidin is a \u201cfire alarm\u201d, generating protective NLRP3-dependent airway epithelial cell inflammatory responses during infection with Pseudomonas aeruginosa. PLoS Pathog., 15.","DOI":"10.1371\/journal.ppat.1007694"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"10957","DOI":"10.1007\/s11033-012-1997-x","article-title":"Cathelicidins: Family of antimicrobial peptides. A review","volume":"39","author":"Lisowski","year":"2012","journal-title":"Mol. Biol. Rep."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2106","DOI":"10.1038\/ncomms3106","article-title":"Bacterial colonization dampens influenza-mediated acute lung injury via induction of M2 alveolar macrophages","volume":"4","author":"Wang","year":"2013","journal-title":"Nat. Commun."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e00483-23","DOI":"10.1128\/iai.00483-23","article-title":"Cathelicidin boosts the antifungal activity of neutrophils and improves prognosis during Aspergillus fumigatus keratitis","volume":"92","author":"Hou","year":"2024","journal-title":"Infect. Immun."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.it.2013.02.008","article-title":"Pattern recognition receptor function in neutrophils","volume":"34","author":"Thomas","year":"2013","journal-title":"Trends Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1111\/imr.13151","article-title":"G protein coupled pattern recognition receptors expressed in neutrophils: Recognition, activation\/modulation, signaling and receptor regulated functions","volume":"314","author":"Dahlgren","year":"2023","journal-title":"Immunol. Rev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1007\/s12016-020-08804-7","article-title":"A Review of Neutrophil Extracellular Traps (NETs) in Disease: Potential Anti-NETs Therapeutics","volume":"61","author":"Mutua","year":"2021","journal-title":"Clin. Rev. Allergy Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Das, T., and Manefield, M. (2012). Pyocyanin promotes extracellular DNA release in Pseudomonas aeruginosa. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0046718"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1016\/j.chom.2019.02.007","article-title":"Neutrophil Extracellular Traps Confine Pseudomonas aeruginosa Ocular Biofilms and Restrict Brain Invasion","volume":"25","author":"Thanabalasuriar","year":"2019","journal-title":"Cell Host Microbe"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Halverson, T.W., Wilton, M., Poon, K.K., Petri, B., and Lewenza, S. (2015). DNA is an antimicrobial component of neutrophil extracellular traps. PLoS Pathog., 11.","DOI":"10.1371\/journal.ppat.1004593"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.intimp.2016.04.044","article-title":"Pseudomonas aeruginosa promotes autophagy to suppress macrophage-mediated bacterial eradication","volume":"38","author":"Wu","year":"2016","journal-title":"Int. Immunopharmacol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1093\/jleuko\/qiae112","article-title":"The role of cathelicidins in neutrophil biology","volume":"116","author":"Yoon","year":"2024","journal-title":"J. Leukoc. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e01660-16","DOI":"10.1128\/AAC.01660-16","article-title":"The Mechanism of Killing by the Proline-Rich Peptide Bac7(1-35) against Clinical Strains of Pseudomonas aeruginosa Differs from That against Other Gram-Negative Bacteria","volume":"61","author":"Runti","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Wan, X., Wang, W., Zhu, J., and Xiao, Y. (2024). Antibacterial peptide Reg4 ameliorates Pseudomonas aeruginosa-induced pulmonary inflammation and fibrosis. Microbiol. Spectr., 12.","DOI":"10.1128\/spectrum.03905-23"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"6402","DOI":"10.4049\/jimmunol.1102185","article-title":"Cathelicidin LL-37 increases lung epithelial cell stiffness, decreases transepithelial permeability, and prevents epithelial invasion by Pseudomonas aeruginosa","volume":"187","author":"Byfield","year":"2011","journal-title":"J. Immunol."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/7\/908\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:55:24Z","timestamp":1760032524000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/7\/908"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,20]]},"references-count":33,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["biom15070908"],"URL":"https:\/\/doi.org\/10.3390\/biom15070908","relation":{},"ISSN":["2218-273X"],"issn-type":[{"type":"electronic","value":"2218-273X"}],"subject":[],"published":{"date-parts":[[2025,6,20]]}}}