{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T14:36:02Z","timestamp":1787582162902,"version":"build-2736575974"},"reference-count":50,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Curr. Issues Mol. Biol.","CIMB"],"abstract":"<jats:p>Mosquito antimicrobial peptides (AMPs) contribute to innate defense against bacteria, fungi, parasites, and, in some experimental contexts, arboviruses. This narrative review evaluates endogenous mosquito AMP families across Aedes, Anopheles, and Culex species and clearly separates them from heterologous peptides introduced into mosquitoes for transmission-blocking studies. The best-supported endogenous families are cecropins, defensins, gambicin, attacin, and diptericin, although gene repertoires vary among mosquito lineages. Mechanistic evidence is strongest for membrane interaction by individual cecropins and defensins. Evidence for intracellular or redox mechanisms is more limited and peptide- and assay-specific; for example, mitochondrial effects have been demonstrated for Anopheles albimanus cecropin 3 in isolated rat cardiac mitochondria, whereas DNA binding and membrane permeabilization have been shown for an Aedes aegypti cecropin A derivative in Pseudomonas aeruginosa. Scorpine, magainin, and human defensin 5 are not mosquito AMPs and are considered separately as heterologous antiplasmodial effectors. Toll and immune deficiency (IMD) pathways regulate mosquito immune genes through NF-\u03baB-family transcription factors, whereas Janus kinase\u2013signal transducer and activator of transcription (JAK\u2013STAT) is a distinct cytokine-signaling pathway. Translational approaches\u2014including transgenic expression, paratransgenesis, Wolbachia-based control, and peptide engineering\u2014remain promising but require cautious interpretation because efficacy, mechanism, ecological safety, horizontal gene transfer, regulatory oversight, and durability have not been resolved uniformly. By distinguishing direct peptide activity from genetic, expression-only, and inferential evidence, this review provides a more rigorous framework for evaluating mosquito AMPs and their potential use in vector-borne disease control.<\/jats:p>","DOI":"10.3390\/cimb48090856","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T13:20:43Z","timestamp":1787577643000},"page":"856","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mosquito Antimicrobial Peptides: Molecular Diversity, Mechanisms of Action, and Translational Potential"],"prefix":"10.3390","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-4101-8693","authenticated-orcid":false,"given":"Yijie","family":"Xiao","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Naval Medical University, Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinhao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Naval Medical University, Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huchen","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Naval Medical University, Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinqian","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Naval Medical University, Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenxia","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Naval Medical University, Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolong","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Naval Medical University, Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-3727-3605","authenticated-orcid":false,"given":"Li","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Naval Medical University, Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lianghua","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Naval Medical University, Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,24]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2025). World Malaria Report 2025: Addressing the Threat of Antimalarial Drug Resistance, WHO."},{"key":"ref_2","unstructured":"World Health Organization (2026, August 12). Dengue and Severe Dengue. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/dengue-and-severe-dengue."},{"key":"ref_3","unstructured":"World Health Organization (2025). WHO Guidelines for Malaria, 13 August 2025, WHO."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"20230063","DOI":"10.1098\/rstb.2023.0063","article-title":"Innate Immunity in Aedes Mosquitoes: From Pathogen Resistance to Shaping the Microbiota","volume":"379","author":"Hixson","year":"2024","journal-title":"Philos. Trans. R. Soc. B"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1738","DOI":"10.1126\/science.1139862","article-title":"Evolutionary Dynamics of Immune-Related Genes and Pathways in Disease-Vector Mosquitoes","volume":"316","author":"Waterhouse","year":"2007","journal-title":"Science"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1462-5822.2009.01388.x","article-title":"Anopheles gambiae Innate Immunity","volume":"12","author":"Yassine","year":"2010","journal-title":"Cell. Microbiol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Zhang, R., Zhu, Y., Pang, X., Xiao, X., Zhang, R., and Cheng, G. (2017). Regulation of Antimicrobial Peptides in Aedes aegypti Aag2 Cells. Front. Cell. Infect. Microbiol., 7.","DOI":"10.3389\/fcimb.2017.00022"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1126\/science.1077136","article-title":"Immunity-Related Genes and Gene Families in Anopheles gambiae","volume":"298","author":"Christophides","year":"2002","journal-title":"Science"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Ramirez, J.L., Hampton, K.J., Rosales, A.M., and Muturi, E.J. (2023). Multiple Mosquito AMPs Are Needed to Potentiate Their Antifungal Effect Against Entomopathogenic Fungi. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.1062383"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"20092","DOI":"10.1074\/jbc.274.29.20092","article-title":"Antimicrobial Activity Spectrum, cDNA Cloning, and mRNA Expression of a Newly Isolated Member of the Cecropin Family from the Mosquito Vector Aedes aegypti","volume":"274","author":"Lowenberger","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e00686-17","DOI":"10.1128\/AAC.00686-17","article-title":"Synergistic Efficacy of Aedes aegypti Antimicrobial Peptide Cecropin A2 and Tetracycline Against Pseudomonas aeruginosa","volume":"61","author":"Zheng","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1046\/j.1365-2583.2000.00164.x","article-title":"Cloning and Analysis of a Cecropin Gene from the Malaria Vector Mosquito, Anopheles gambiae","volume":"9","author":"Vizioli","year":"2000","journal-title":"Insect Mol. Biol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Luplertlop, N., Surasombatpattana, P., Patramool, S., Dumas, E., Wasinpiyamongkol, L., Saune, L., Hamel, R., Bernard, E., Sereno, D., and Thomas, F. (2011). Induction of a Peptide with Activity Against a Broad Spectrum of Pathogens in the Aedes aegypti Salivary Gland, Following Infection with Dengue Virus. PLoS Pathog., 7.","DOI":"10.1371\/journal.ppat.1001252"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Godreuil, S., Leban, N., Padilla, A., Hamel, R., Luplertlop, N., Chauffour, A., Vittecoq, M., Hoh, F., Thomas, F., and Sougakoff, W. (2014). Aedesin: Structure and Antimicrobial Activity Against Multidrug Resistant Bacterial Strains. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0105441"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1098\/rspb.1995.0139","article-title":"Full Sequence and Characterization of Two Insect Defensins: Immune Peptides from the Mosquito Aedes aegypti","volume":"261","author":"Chalk","year":"1995","journal-title":"Proc. R. Soc. Lond. B"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1016\/j.dci.2012.01.005","article-title":"Increased Survivorship Following Bacterial Infection by the Mosquito Aedes aegypti as Compared with Anopheles gambiae Correlates with Increased Transcriptional Induction of Antimicrobial Peptides","volume":"37","author":"Coggins","year":"2012","journal-title":"Dev. Comp. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/S0965-1748(00)00143-0","article-title":"The Defensin Peptide of the Malaria Vector Mosquito Anopheles gambiae: Antimicrobial Activities and Expression in Adult Mosquitoes","volume":"31","author":"Vizioli","year":"2001","journal-title":"Insect Biochem. Mol. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1093\/embo-reports\/kvf180","article-title":"Reverse Genetics in the Mosquito Anopheles gambiae: Targeted Disruption of the Defensin Gene","volume":"3","author":"Blandin","year":"2002","journal-title":"EMBO Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"12630","DOI":"10.1073\/pnas.221466798","article-title":"Gambicin: A Novel Immune Responsive Antimicrobial Peptide from the Malaria Vector Anopheles gambiae","volume":"98","author":"Vizioli","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Buonocore, F., Fausto, A.M., Della Pelle, G., Roncevic, T., Gerdol, M., and Picchietti, S. (2021). Attacins: A Promising Class of Insect Antimicrobial Peptides. Antibiotics, 10.","DOI":"10.3390\/antibiotics10020212"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e00311-24","DOI":"10.1128\/aac.00311-24","article-title":"Antimalarial Activity of Cecropin Antimicrobial Peptides Derived from Anopheles Mosquitoes","volume":"68","author":"Lou","year":"2024","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/S0014-5793(00)01384-3","article-title":"Scorpine, an Anti-Malaria and Anti-Bacterial Agent Purified from Scorpion Venom","volume":"471","author":"Conde","year":"2000","journal-title":"FEBS Lett."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Grogan, C., Bennett, M., Moore, S., and Lampe, D. (2021). Novel Asaia bogorensis Signal Sequences for Plasmodium Inhibition in Anopheles stephensi. Front. Microbiol., 12.","DOI":"10.3389\/fmicb.2021.633667"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Grogan, C., Bennett, M., and Lampe, D.J. (2022). An Evaluation of Fusion Partner Proteins for Paratransgenesis in Asaia bogorensis. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0273568"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2628","DOI":"10.1128\/iai.57.9.2628-2633.1989","article-title":"Effects of Magainins and Cecropins on the Sporogonic Development of Malaria Parasites in Mosquitoes","volume":"57","author":"Gwadz","year":"1989","journal-title":"Infect. Immun."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Liu, T., Wang, J., Li, X., Yu, S., Zheng, D., Liu, Z., Yang, X., and Wang, Y. (2024). Human Defensin 5 Inhibits Plasmodium yoelii Development in Anopheles stephensi by Promoting Innate Immune Response. Trop. Med. Infect. Dis., 9.","DOI":"10.3390\/tropicalmed9080169"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1038\/nrmicro1098","article-title":"Antimicrobial Peptides: Pore Formers or Metabolic Inhibitors in Bacteria?","volume":"3","author":"Brogden","year":"2005","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1021\/cb1001558","article-title":"Describing the Mechanism of Antimicrobial Peptide Action with the Interfacial Activity Model","volume":"5","author":"Wimley","year":"2010","journal-title":"ACS Chem. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1016\/j.bbamem.2006.02.021","article-title":"Peptide\u2013Membrane Interactions and Mechanisms of Membrane Destruction by Amphipathic \u03b1-Helical Antimicrobial Peptides","volume":"1758","author":"Sato","year":"2006","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.peptides.2013.07.010","article-title":"Mitochondrial Inactivation by Anopheles albimanus Cecropin 3: Molecular Mechanisms","volume":"53","year":"2014","journal-title":"Peptides"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"16395","DOI":"10.1038\/s41598-017-16625-6","article-title":"Involvement of Cecropin B in the Formation of the Aedes aegypti Mosquito Cuticle","volume":"7","author":"Liu","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"E23","DOI":"10.1073\/pnas.1116932108","article-title":"Wolbachia Induces Reactive Oxygen Species (ROS)-Dependent Activation of the Toll Pathway to Control Dengue Virus in the Mosquito Aedes aegypti","volume":"109","author":"Pan","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1006\/expr.1999.4350","article-title":"Mosquito\u2013Plasmodium Interactions in Response to Immune Activation of the Vector","volume":"91","author":"Lowenberger","year":"1999","journal-title":"Exp. Parasitol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"8111","DOI":"10.1073\/pnas.1003056107","article-title":"Blocking of Plasmodium Transmission by Cooperative Action of Cecropin A and Defensin A in Transgenic Aedes aegypti Mosquitoes","volume":"107","author":"Kokoza","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Ramirez, J.L., Dunlap, C.A., Muturi, E.J., Barletta, A.B.F., and Rooney, A.P. (2018). Entomopathogenic Fungal Infection Leads to Temporospatial Modulation of the Mosquito Immune System. PLoS Negl. Trop. Dis., 12.","DOI":"10.1371\/journal.pntd.0006433"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4479","DOI":"10.3390\/v6114479","article-title":"Mosquito Immunity Against Arboviruses","volume":"6","author":"Sim","year":"2014","journal-title":"Viruses"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Liu, W.-Q., Chen, S.-Q., Bai, H.-Q., Wei, Q.-M., Zhang, S.-N., Chen, C., Zhu, Y.-H., Yi, T.-W., Guo, X.-P., and Chen, X.-Y. (2020). The Ras\/ERK Signaling Pathway Couples Antimicrobial Peptides to Mediate Resistance to Dengue Virus in Aedes Mosquitoes. PLoS Negl. Trop. Dis., 14.","DOI":"10.1371\/journal.pntd.0008660"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Kumar, A., Srivastava, P., Sirisena, P., Dubey, S.K., Kumar, R., Shrinet, J., and Sunil, S. (2018). Mosquito Innate Immunity. Insects, 9.","DOI":"10.3390\/insects9030095"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Meister, S., Agianian, B., Turlure, F., Rel\u00f3gio, A., Morlais, I., Kafatos, F.C., and Christophides, G.K. (2009). Anopheles gambiae PGRPLC-Mediated Defense Against Bacteria Modulates Infections with Malaria Parasites. PLoS Pathog., 5.","DOI":"10.1371\/journal.ppat.1000542"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.ibmb.2009.01.007","article-title":"The Role of NF-\u03baB Factor REL2 in the Aedes aegypti Immune Response","volume":"39","author":"Antonova","year":"2009","journal-title":"Insect Biochem. Mol. Biol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Russell, T.A., Ayaz, A., Davidson, A.D., Fernandez-Sesma, A., and Maringer, K. (2021). Imd Pathway-Specific Immune Assays Reveal NF-\u03baB Stimulation by Viral RNA PAMPs in Aedes aegypti Aag2 Cells. PLoS Negl. Trop. Dis., 15.","DOI":"10.1371\/journal.pntd.0008524"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Jupatanakul, N., Sim, S., Angler\u00f3-Rodr\u00edguez, Y.I., Souza-Neto, J., Das, S., Poti, K.E., Rossi, S.L., Bergren, N., Vasilakis, N., and Dimopoulos, G. (2017). Engineered Aedes aegypti JAK\/STAT Pathway-Mediated Immunity to Dengue Virus. PLoS Negl. Trop. Dis., 11.","DOI":"10.1371\/journal.pntd.0005187"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Kim, I.H., Castillo, J.C., Aryan, A., Martin-Martin, I., Nouzova, M., Noriega, F.G., Barletta, A.B.F., Calvo, E., Adelman, Z.N., and Ribeiro, J.M.C. (2020). A Mosquito Juvenile Hormone Binding Protein (mJHBP) Regulates the Activation of Innate Immune Defenses and Hemocyte Development. PLoS Pathog., 16.","DOI":"10.1371\/journal.ppat.1008288"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Ramirez, J.L., Souza-Neto, J., Torres Cosme, R., Rovira, J., Ortiz, A., Pascale, J.M., and Dimopoulos, G. (2012). Reciprocal Tripartite Interactions between the Aedes aegypti Midgut Microbiota, Innate Immune System and Dengue Virus Influences Vector Competence. PLoS Negl. Trop. Dis., 6.","DOI":"10.1371\/journal.pntd.0001561"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1038\/s42003-023-05516-4","article-title":"Nutritional Stress Compromises Mosquito Fitness and Antiviral Immunity, While Enhancing Dengue Virus Infection Susceptibility","volume":"6","author":"Yan","year":"2023","journal-title":"Commun. Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1186\/s13071-016-1427-3","article-title":"Paratransgenesis to Control Malaria Vectors: A Semi-Field Pilot Study","volume":"9","author":"Mancini","year":"2016","journal-title":"Parasit. Vectors"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1186\/s13071-021-05132-3","article-title":"Overview of Paratransgenesis as a Strategy to Control Pathogen Transmission by Insect Vectors","volume":"15","author":"Ratcliffe","year":"2022","journal-title":"Parasit. Vectors"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2177","DOI":"10.1056\/NEJMoa2030243","article-title":"Efficacy of Wolbachia-Infected Mosquito Deployments for the Control of Dengue","volume":"384","author":"Utarini","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Lindsey, A.R.I. (2020). Sensing, Signaling, and Secretion: A Review and Analysis of Systems for Regulating Host Interaction in Wolbachia. Genes, 11.","DOI":"10.3390\/genes11070813"},{"key":"ref_50","unstructured":"World Health Organization (2026, August 12). WHO Update on the Assessment of Wolbachia Population Replacement for the Control of Aedes-Borne Diseases. Available online: https:\/\/www.who.int\/news\/item\/11-06-2026-who-update-on-the-assessment-of-wolbachia-population-replacement-for-the-control-of-aedes-borne-diseases."}],"container-title":["Current Issues in Molecular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1467-3045\/48\/9\/856\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T13:54:50Z","timestamp":1787579690000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1467-3045\/48\/9\/856"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,24]]},"references-count":50,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["cimb48090856"],"URL":"https:\/\/doi.org\/10.3390\/cimb48090856","relation":{},"ISSN":["1467-3045"],"issn-type":[{"value":"1467-3045","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,24]]}}}