{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T01:57:02Z","timestamp":1784599022063,"version":"3.55.0"},"reference-count":125,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,8,15]],"date-time":"2022-08-15T00:00:00Z","timestamp":1660521600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003141","name":"Consejo Nacional de Ciencia y Tecnolog\u00eda, Mexico","doi-asserted-by":"publisher","award":["A1-S-8989"],"award-info":[{"award-number":["A1-S-8989"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Parasites and other eventually pathogenic organisms require the ability to adapt to different environmental conditions inside the host to assure survival. Some host proteins have evolved as defense constituents, such as lactoferrin (Lf), which is part of the innate immune system. Lf in its iron-free form (apo-Lf) and its peptides obtained by cleavage with pepsin are microbicides. Parasites confront Lf in mucosae and blood. In this work, the activity of Lf against pathogenic and opportunistic parasites such as Cryptosporidium spp., Eimeria spp., Entamoeba histolytica, Giardia duodenalis, Leishmania spp., Trypanosoma spp., Plasmodium spp., Babesia spp., Toxoplasma gondii, Trichomonas spp., and the free-living but opportunistic pathogens Naegleria fowleri and Acanthamoeba castellani were reviewed. The major effects of Lf could be the inhibition produced by sequestering the iron needed for their survival and the production of oxygen-free radicals to more complicated mechanisms, such as the activation of macrophages to phagocytes with the posterior death of those parasites. Due to the great interest in Lf in the fight against pathogens, it is necessary to understand the exact mechanisms used by this protein to affect their virulence factors and to kill them.<\/jats:p>","DOI":"10.3390\/pharmaceutics14081702","type":"journal-article","created":{"date-parts":[[2022,8,15]],"date-time":"2022-08-15T23:44:03Z","timestamp":1660607043000},"page":"1702","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Activity of Apo-Lactoferrin on Pathogenic Protozoa"],"prefix":"10.3390","volume":"14","author":[{"given":"Magda","family":"Reyes-L\u00f3pez","sequence":"first","affiliation":[{"name":"Departamento de Biolog\u00eda Celular, Centro de Investigaci\u00f3n y de Estudios Avanzados del Instituto Polit\u00e9cnico Nacional (CINVESTAV-IPN), Mexico City 07360, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerardo","family":"Ram\u00edrez-Rico","sequence":"additional","affiliation":[{"name":"Departamento de Biolog\u00eda Celular, Centro de Investigaci\u00f3n y de Estudios Avanzados del Instituto Polit\u00e9cnico Nacional (CINVESTAV-IPN), Mexico City 07360, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2725-5743","authenticated-orcid":false,"given":"Jes\u00fas","family":"Serrano-Luna","sequence":"additional","affiliation":[{"name":"Departamento de Biolog\u00eda Celular, Centro de Investigaci\u00f3n y de Estudios Avanzados del Instituto Polit\u00e9cnico Nacional (CINVESTAV-IPN), Mexico City 07360, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mireya","family":"de la Garza","sequence":"additional","affiliation":[{"name":"Departamento de Biolog\u00eda Celular, Centro de Investigaci\u00f3n y de Estudios Avanzados del Instituto Polit\u00e9cnico Nacional (CINVESTAV-IPN), Mexico City 07360, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1016\/S0020-7519(01)00259-4","article-title":"Life in vacuoles\u2014Nutrient acquisition by Leishmania amastigotes","volume":"31","author":"Burchmore","year":"2001","journal-title":"Int. J. Parasitol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1128\/EC.00287-10","article-title":"Nutrient Transport and Pathogenesis in Selected Parasitic Protozoa","volume":"10","author":"Landfear","year":"2011","journal-title":"Eukaryot. Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1128\/EC.00004-08","article-title":"The Nascent Parasitophorous Vacuole Membrane of Encephalitozoon cuniculi Is Formed by Host Cell Lipids and Contains Pores which Allow Nutrient Uptake","volume":"7","author":"Gross","year":"2008","journal-title":"Eukaryot. Cell"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"12998","DOI":"10.1073\/pnas.0903831106","article-title":"Host-derived glucose and its transporter in the obligate intracellular pathogen Toxoplasma gondii are dispensable by glutaminolysis","volume":"106","author":"Blume","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/j.bcp.2003.09.005","article-title":"Interaction of substituted hexose analogues with the Trypanosoma brucei hexose transporter","volume":"67","author":"Azema","year":"2004","journal-title":"Biochem. Pharmacol."},{"key":"ref_6","first-page":"2633","article-title":"Bovine Lactoferrin and Lactoferrin-Derived Peptides Inhibit the Growth of Vibrio cholerae and Other Vibrio species","volume":"8","author":"Bolscher","year":"2017","journal-title":"Front. Microbiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1111\/j.1600-065X.2010.00990.x","article-title":"Invasion and intracellular survival by protozoan parasites","volume":"240","author":"Sibley","year":"2011","journal-title":"Immunol. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1111\/j.1462-5822.2009.01417.x","article-title":"Modelling parasite dissemination: Host cell subversion and immune evasion by Toxoplasma gondii","volume":"12","author":"Lambert","year":"2010","journal-title":"Cell. Microbiol."},{"key":"ref_9","first-page":"130","article-title":"Identification of the bactericidal domain of lactoferrin","volume":"1121","author":"Bellamy","year":"1992","journal-title":"Biochim. Biophys. Acta BBA-Protein Struct. Mol. Enzym."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Gruden, \u0160., and Ulrih, N.P. (2021). Diverse Mechanisms of Antimicrobial Activities of Lactoferrins, Lactoferricins, and Other Lactoferrin-Derived Peptides. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222011264"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Bruni, N., Capucchio, M.T., Biasibetti, E., Pessione, E., Cirrincione, S., Giraudo, L., Corona, A., and Dosio, F. (2016). Antimicrobial Activity of Lactoferrin-Related Peptides and Applications in Human and Veterinary Medicine. Molecules, 21.","DOI":"10.3390\/molecules21060752"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Zarzosa-Moreno, D., Avalos-G\u00f3mez, C., Ram\u00edrez-Texcalco, L.S., Torres-L\u00f3pez, E., Ram\u00edrez-Mondrag\u00f3n, R., Hern\u00e1ndez-Ram\u00edrez, J.O., Serrano-Luna, J., and De La Garza, M. (2020). Lactoferrin and Its Derived Peptides: An Alternative for Combating Virulence Mechanisms Developed by Pathogens. Molecules, 25.","DOI":"10.3390\/molecules25245763"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1128\/iai.61.2.719-728.1993","article-title":"Antibacterial activity of lactoferrin and a pepsin-derived lactoferrin peptide fragment","volume":"61","author":"Yamauchi","year":"1993","journal-title":"Infect. Immun."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2588","DOI":"10.1007\/s00018-005-5373-z","article-title":"Lactoferricin: A lactoferrin-derived peptide with antimicrobial, antiviral, antitumor and immunological properties","volume":"62","author":"Gifford","year":"2005","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"149","DOI":"10.2217\/fmb.11.140","article-title":"Iron-saturated lactoferrin and pathogenic protozoa: Could this protein be an iron source for their parasitic style of life?","volume":"7","year":"2012","journal-title":"Future Microbiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.2147\/IDR.S177997","article-title":"Genetic variation in metronidazole metabolism and oxidative stress pathways in clinical Giardia lamblia assemblage A and B isolates","volume":"12","author":"Saghaug","year":"2019","journal-title":"Infect. Drug Resist."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1017\/S0031182017002025","article-title":"A review on metronidazole: An old warhorse in antimicrobial chemotherapy","volume":"146","author":"Leitsch","year":"2019","journal-title":"Parasitology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"834008","DOI":"10.3389\/fmicb.2022.834008","article-title":"Characterization of Metronidazole-Resistant Giardia intestinalis Lines by Comparative Transcriptomics and Proteomics","volume":"13","author":"Krakovka","year":"2022","journal-title":"Front. Microbiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1128\/CMR.14.1.150-164.2001","article-title":"Drug Targets and Mechanisms of Resistance in the Anaerobic Protozoa","volume":"14","author":"Upcroft","year":"2001","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1128\/CMR.17.4.783-793.2004","article-title":"Treatment of Infections Caused by Metronidazole-Resistant Trichomonas vaginalis","volume":"17","author":"Cudmore","year":"2004","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"181","DOI":"10.2174\/157488470903140806112509","article-title":"Development of natural products as anti-parasitic agents","volume":"9","author":"Monzote","year":"2014","journal-title":"Curr. Clin. Pharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1827","DOI":"10.2174\/0929867013371563","article-title":"New Trends in Extraction, Identification and Quantification of Artemisinin and its Derivatives","volume":"8","author":"Christen","year":"2001","journal-title":"Curr. Med. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/j.pt.2021.04.006","article-title":"Assessing risks of Plasmodium falciparum resistance to select next-generation antimalarials","volume":"37","author":"Duffey","year":"2021","journal-title":"Trends Parasitol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1016\/j.pt.2018.07.009","article-title":"Genetic Diversity and Population Structure of Cryptosporidium","volume":"34","author":"Feng","year":"2018","journal-title":"Trends Parasitol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.actatropica.2018.08.018","article-title":"Widespread occurrence of Cryptosporidium infections in patients with HIV\/AIDS: Epidemiology, clinical feature, diagnosis, and therapy","volume":"187","author":"Wang","year":"2018","journal-title":"Acta Trop."},{"key":"ref_26","unstructured":"Janssen, B., and Snowden, J. (2022). Cryptosporidiosis. StatPearls, Stat Pearls Publishing."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1046\/j.1365-2672.2002.01762.x","article-title":"Antibacterial activity of pepsin-digested lactoferrin on foodborne pathogens in buffered broth systems and ultra-high temperature milk with EDTA","volume":"93","author":"Murdock","year":"2002","journal-title":"J. Appl. Microbiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1645\/GE-2822.1","article-title":"Phospholipases and Cationic Peptides Inhibit Cryptosporidium parvum Sporozoite Infectivity by Parasiticidal and Non-Parasiticidal Mechanisms","volume":"98","author":"Carryn","year":"2012","journal-title":"J. Parasitol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"774","DOI":"10.4269\/ajtmh.16-0804","article-title":"Killing of Cryptosporidium sporozoites by Lactoferrin","volume":"97","author":"Paredes","year":"2017","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.vetpar.2015.05.007","article-title":"Eimeria genomics: Where are we now and where are we going?","volume":"212","author":"Blake","year":"2015","journal-title":"Vet. Parasitol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/j.parint.2014.10.005","article-title":"Phylogeny and evolution of apicoplasts and apicomplexan parasites","volume":"64","author":"Arisue","year":"2015","journal-title":"Parasitol. Int."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.1017\/S0031182013000838","article-title":"Sex and Eimeria: A molecular perspective","volume":"140","author":"Walker","year":"2013","journal-title":"Parasitology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1017\/S0031182019001562","article-title":"Life cycle stages, specific organelles and invasion mechanisms of Eimeria species","volume":"147","author":"Burrell","year":"2020","journal-title":"Parasitology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/s13071-022-05159-0","article-title":"Eimeria proteins: Order amidst disorder","volume":"15","author":"Olajide","year":"2022","journal-title":"Parasites Vectors"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1292\/jvms.63.187","article-title":"Reduction of the Infectivity of Toxoplasma gondii and Eimeria stiedai Sporozoites by Treatment with Bovine Lactoferricin","volume":"63","author":"Omata","year":"2001","journal-title":"J. Vet. Med. Sci."},{"key":"ref_36","unstructured":"World Health Organization (1997). Amoebiasis = Amibiase. Wkly. Epidemiol. Rec. Relev. \u00c9pid\u00e9miol. Hebd., 72, 97\u201399."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1016\/S0140-6736(03)12830-9","article-title":"Amoebiasis","volume":"361","author":"Stanley","year":"2003","journal-title":"Lancet"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"151358","DOI":"10.1016\/j.ijmm.2019.151358","article-title":"Intestinal amoebiasis: 160 years of its first detection and still remains as a health problem in developing countries","volume":"310","author":"Carrero","year":"2020","journal-title":"Int. J. Med. Microbiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1146\/annurev-micro-091313-103550","article-title":"Regulation of Virulence of Entamoeba histolytica","volume":"68","author":"Marie","year":"2014","journal-title":"Annu. Rev. Microbiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1136\/bmj.280.6228.1351","article-title":"The salutary effect of milk on amoebiasis and its reversal by iron","volume":"280","author":"Murray","year":"1980","journal-title":"Br. Med. J."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1136\/bmj.1.4821.1200","article-title":"Effect of Milk Diet on P. cynomolgi Infections in Monkeys","volume":"1","author":"Bray","year":"1953","journal-title":"Br. Med. J."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"114","DOI":"10.2174\/187152109787846105","article-title":"Antifungal and Antiparasitic Activities of Lactoferrin","volume":"8","author":"Leboffe","year":"2009","journal-title":"Anti-Infect. Agents Med. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/0014-4894(65)90022-6","article-title":"An iron-requirement for growth of Entamoeba histolytica in culture, and the antiamebal activity of 7-iodo-8-hydroxy-quinoline-5-sulfonic acid","volume":"17","author":"Latour","year":"1965","journal-title":"Exp. Parasitol."},{"key":"ref_44","unstructured":"Serrano, J.J., Arzola, N.J., Reyes, M., de la Garza, M., and Serrano-Luna, J. (1998, January 24\u201326). Iron and Entamoeba histolytica HM1:IMSS. Proceedings of the IX International Congress of Parasitoly ICOPA IX Makuhari Messe, Chiba, Japan."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.1126\/science.6310751","article-title":"Human Milk Kills Parasitic Intestinal Protozoa","volume":"221","author":"Gillin","year":"1983","journal-title":"Science"},{"key":"ref_46","first-page":"327","article-title":"Microbicidal action of lactoferrin and lactoferricin and their synergistic effect with metronidazole in Entamoeba histolytica","volume":"84","year":"2006","journal-title":"Biochem. Cell Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1099\/00222615-47-9-837","article-title":"Synergic antistaphylococcal properties of lactoferrin and lysozyme","volume":"47","author":"Leitch","year":"1998","journal-title":"J. Med. Microbiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"S116","DOI":"10.1016\/j.ypmed.2011.12.023","article-title":"A novel extract from bovine colostrum whey supports anti-bacterial and anti-viral innate immune functions in vitro and in vivo: I. Enhanced immune activity in vitro translates to improved microbial clearance in animal infection models","volume":"54","author":"Benson","year":"2012","journal-title":"Prev. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1093\/tropej\/46.2.92","article-title":"Inhibitory factors in breastmilk, maternal and infant sera against in vitro growth of Plasmodium falciparum malaria parasite","volume":"46","author":"Kassim","year":"2000","journal-title":"J. Trop. Pediatr."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.micpath.2017.10.056","article-title":"Treatment strategy by lactoperoxidase and lactoferrin combination: Immunomodulatory and antibacterial activity against multidrug-resistant Acinetobacter baumannii","volume":"114","author":"Mahdi","year":"2018","journal-title":"Microb. Pathog."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"106","DOI":"10.3121\/cmr.4.2.106","article-title":"Amoebicidal Activity of Milk, Apo-lactoferrin, sIgA and Lysozyme","volume":"4","year":"2006","journal-title":"Clin. Med. Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.biochi.2008.05.019","article-title":"Bactericidal activity of LFchimera is stronger and less sensitive to ionic strength than its constituent lactoferricin and lactoferrampin peptides","volume":"91","author":"Bolscher","year":"2009","journal-title":"Biochimie"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1007\/s10534-010-9295-3","article-title":"Microbicidal effect of the lactoferrin peptides Lactoferricin17\u201330, Lactoferrampin265\u2013284, and Lactoferrin chimera on the parasite Entamoeba histolytica","volume":"23","author":"Nazmi","year":"2010","journal-title":"BioMetals"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2635","DOI":"10.1128\/AAC.43.11.2635","article-title":"Synergistic Fungistatic Effects of Lactoferrin in Combination with Antifungal Drugs against Clinical Candida Isolates","volume":"43","author":"Kuipers","year":"1999","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"4522","DOI":"10.1128\/IAI.73.8.4522-4529.2005","article-title":"Resistance to Intestinal Entamoeba histolytica Infection Is Conferred by Innate Immunity and Gr-1+ Cells","volume":"73","author":"Asgharpour","year":"2005","journal-title":"Infect. Immun."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1139\/o2012-008","article-title":"Oral lactoferrin treatment resolves amoebic intracecal infection in C3H\/HeJ mice","volume":"90","author":"Carrero","year":"2012","journal-title":"Biochem. Cell Biol."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Le\u00f3n-Sicairos, N., Ordaz-Pichardo, C., Carrero, J.C., and de la Garza, M. (2017). Lactoferrin in the Battle against Intestinal Parasites: A Review. Natural Remedies in the Fight against Parasites, IntechOpen.","DOI":"10.5772\/66819"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1139\/o11-084","article-title":"Effect of bovine lactoferrin in a therapeutic hamster model of hepatic amoebiasis","volume":"90","year":"2012","journal-title":"Biochem. Cell Biol."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"D\u00edaz-God\u00ednez, C., Gonz\u00e1lez-Galindo, X., Meza-Menchaca, T., Bobes, R.J., de la Garza, M., Le\u00f3n-Sicairos, N., Laclette, J.P., and Carrero, J.C. (2019). Synthetic bovine lactoferrin peptide Lfampin kills Entamoeba histolytica trophozoites by necrosis and resolves amoebic intracecal infection in mice. Biosci. Rep., 39.","DOI":"10.1042\/BSR20180850"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"18020","DOI":"10.1038\/s41598-018-36563-1","article-title":"Lactoferrin and lactoferricin endocytosis halt Giardia cell growth and prevent infective cyst production","volume":"8","author":"Frontera","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"492","DOI":"10.3855\/jidc.9626","article-title":"Hematological profile in natural progression of giardiasis: Kinetics of experimental infection in gerbils","volume":"12","author":"Gil","year":"2018","journal-title":"J. Infect. Dev. Ctries."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1016\/S0140-6736(02)07744-9","article-title":"Effects of stunting, diarrhoeal disease, and parasitic infection during infancy on cognition in late childhood: A follow-up study","volume":"359","author":"Berkman","year":"2002","journal-title":"Lancet"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"4550","DOI":"10.1128\/iai.63.11.4550-4552.1995","article-title":"Giardicidal activity of lactoferrin and N-terminal peptides","volume":"63","author":"Turchany","year":"1995","journal-title":"Infect. Immun."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1111\/j.1550-7408.1997.tb05694.x","article-title":"Ultrastructural Effects of Lactoferrin Binding on Giardia lamblia Trophozoites","volume":"44","author":"Turchany","year":"1997","journal-title":"J. Eukaryot. Microbiol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/j.pt.2011.06.003","article-title":"Cyst and encystment in protozoan parasites: Optimal targets for new life-cycle interrupting strategies?","volume":"27","author":"Carrero","year":"2011","journal-title":"Trends Parasitol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1139\/bcb-2016-0079","article-title":"Parasiticidal effect of synthetic bovine lactoferrin peptides on the enteric parasite Giardia intestinalis","volume":"95","author":"Nazmi","year":"2017","journal-title":"Biochem. Cell Biol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1881","DOI":"10.1086\/588476","article-title":"Impact of Lactoferrin Supplementation on Growth and Prevalence of Giardia Colonization in Children","volume":"46","author":"Ochoa","year":"2008","journal-title":"Clin. Infect. Dis."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1186\/s13071-017-2028-5","article-title":"The history of leishmaniasis","volume":"10","author":"Steverding","year":"2017","journal-title":"Parasites Vectors"},{"key":"ref_69","first-page":"38","article-title":"Leishmaniosis","volume":"68","year":"2017","journal-title":"Rev. Cienc. Acad. Mex. Cienc."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2952","DOI":"10.1128\/iai.60.7.2952-2956.1992","article-title":"Effects of iron limitation on production of a siderophore, outer membrane proteins, and hemolysin and on hydrophobicity, cell adherence, and lethality for mice of Vibrio parahaemolyticus","volume":"60","author":"Dai","year":"1992","journal-title":"Infect. Immun."},{"key":"ref_71","first-page":"213","article-title":"Laboratory cultivation and maintenance of Leishmania","volume":"Volume 1","author":"Chang","year":"1985","journal-title":"Leishmaniasis (Human Parasitic Diseases)"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"3262","DOI":"10.1128\/iai.62.8.3262-3269.1994","article-title":"Acquisition of iron from transferrin and lactoferrin by the protozoan Leishmania chagasi","volume":"62","author":"Wilson","year":"1994","journal-title":"Infect. Immun."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1172\/JCI115461","article-title":"Hydrogen peroxide-mediated toxicity for Leishmania donovani chagasi promastigotes. Role of hydroxyl radical and protection by heat shock","volume":"88","author":"Zarley","year":"1991","journal-title":"J. Clin. Investig."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/S0014-4894(02)00018-8","article-title":"Leishmania chagasi: Uptake of iron bound to lactoferrin or transferrin requires an iron reductase","volume":"100","author":"Wilson","year":"2002","journal-title":"Exp. Parasitol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2265","DOI":"10.1007\/s00726-012-1304-0","article-title":"Enhanced leishmanicidal activity of cryptopeptide chimeras from the active N1 domain of bovine lactoferrin","volume":"43","author":"Silva","year":"2012","journal-title":"Amino Acids"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.2217\/nnm.14.182","article-title":"Targeted chemotherapy of visceral leishmaniasis by lactoferrin-appended amphotericin B-loaded nanoreservoir: In vitro and in vivo studies","volume":"10","author":"Asthana","year":"2015","journal-title":"Nanomedicine"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1016\/j.cyto.2018.05.010","article-title":"Lactoferrin-modified Betulinic Acid-loaded PLGA nanoparticles are strong anti-leishmanials","volume":"110","author":"Halder","year":"2018","journal-title":"Cytokine"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1111\/j.1550-7408.1988.tb04086.x","article-title":"Trypanosoma cruzi: A Specific Surface Marker for the Amastigote Form","volume":"35","author":"Lima","year":"1988","journal-title":"J. Protozool."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"4176","DOI":"10.4049\/jimmunol.134.6.4176","article-title":"Lactoferrin effects on phagocytic cell function. I. Increased uptake and killing of an intracellular parasite by murine macrophages and human monocytes","volume":"134","author":"Lima","year":"1985","journal-title":"J. Immunol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1647","DOI":"10.4049\/jimmunol.139.5.1647","article-title":"Lactoferrin effects of phagocytic cell function. II. The presence of iron is required for the lactoferrin molecule to stimulate intracellular killing by macrophages but not to enhance the uptake of particles and microorganisms","volume":"139","author":"Lima","year":"1987","journal-title":"J. Immunol."},{"key":"ref_81","first-page":"463","article-title":"Neutrophilic granulocytes in acute bacterial infection. Sequential studies on lysozyme, myeloperoxidase and lactoferrin","volume":"26","author":"Hansen","year":"1976","journal-title":"Clin. Exp. Immunol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1292\/jvms.66.619","article-title":"The Detection of Bovine Lactoferrin Binding Protein on Trypanosoma brucei","volume":"66","author":"Tanaka","year":"2004","journal-title":"J. Vet. Med. Sci."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1111\/j.1365-3156.2009.02287.x","article-title":"From malaria control to eradication: The WHO perspective","volume":"14","author":"Mendis","year":"2009","journal-title":"Trop. Med. Int. Health"},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Foth, B.J., Zhang, N., Chaal, B.K., Sze, S.K., Preiser, P.R., and Bozdech, Z. (2011). Quantitative Time-course Profiling of Parasite and Host Cell Proteins in the Human Malaria Parasite Plasmodium falciparum. Mol. Cell. Proteom., 10.","DOI":"10.1074\/mcp.M110.006411"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"7690","DOI":"10.1038\/ncomms8690","article-title":"Plasmodium falciparum full life cycle and Plasmodium ovale liver stages in humanized mice","volume":"6","author":"Soulard","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0014-4894(87)90072-5","article-title":"Plasmodium falciparum: Inhibition in vitro with lactoferrin, desferriferrithiocin, and desferricrocin","volume":"63","author":"Fritsch","year":"1987","journal-title":"Exp. Parasitol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1699","DOI":"10.1084\/jem.184.5.1699","article-title":"Dual interaction of the malaria circumsporozoite protein with the low density lipoprotein receptor-related protein (LRP) and heparan sulfate proteoglycans","volume":"184","author":"Shakibaei","year":"1996","journal-title":"J. Exp. Med."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1084\/jem.184.3.945","article-title":"Remnant lipoproteins inhibit malaria sporozoite invasion of hepatocytes","volume":"184","author":"Sinnis","year":"1996","journal-title":"J. Exp. Med."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1182\/blood.V94.1.326.413a32_326_332","article-title":"Inhibitory activity of human lactoferrin and its peptide on chondroitin sulfate A-, CD36-, and thrombospondin-mediated cytoadherence of Plasmodium falciparum-infected erythrocytes","volume":"94","author":"Eda","year":"1999","journal-title":"Blood"},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Parra, M., Liu, X., Derrick, S.C., Yang, A., Tian, J., Kolibab, K., Kumar, S., and Morris, S.L. (2013). Molecular Analysis of Non-Specific Protection against Murine Malaria Induced by BCG Vaccination. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0066115"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"47","DOI":"10.2217\/nnm.15.181","article-title":"Antiparasitic and immunomodulatory potential of oral nanocapsules encapsulated lactoferrin protein against Plasmodium berghei","volume":"11","author":"Anand","year":"2016","journal-title":"Nanomedicine"},{"key":"ref_92","first-page":"11","article-title":"Piroplasmosis in man; report of a case","volume":"9","author":"Skrabalo","year":"1957","journal-title":"Doc. Med. Geogr. Trop."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Montero, E., Gray, J., Lobo, C.A., and Gonz\u00e1lez, L.M. (2022). Babesia and Human Babesiosis. Pathogens, 11.","DOI":"10.3390\/pathogens11040399"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1111\/mmi.14650","article-title":"A framework for signaling throughout the life cycle of Babesia species","volume":"115","author":"Elsworth","year":"2021","journal-title":"Mol. Microbiol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"710","DOI":"10.4269\/ajtmh.2005.73.710","article-title":"Inhibitory effect of lactoferrin on in vitro growth of Babesia caballi","volume":"73","author":"Ikadai","year":"2005","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"113","DOI":"10.7883\/yoken.JJID.2015.023","article-title":"In Vivo Efficacy of Drugs against Toxoplasma gondii Combined with Immunomodulators","volume":"69","author":"Yanik","year":"2016","journal-title":"Jpn. J. Infect. Dis."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1084\/jem.136.5.1157","article-title":"The interaction between Toxoplasma gondii and mammalian cells. I. Mechanism of entry and intracellular fate of the parasite","volume":"136","author":"Jones","year":"1972","journal-title":"J. Exp. Med."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1590\/S0037-86822002000100001","article-title":"Prenatal toxoplasmosis diagnosis from amniotic fluid by PCR","volume":"35","author":"Vidigal","year":"2002","journal-title":"Rev. Soc. Bras. Med. Trop."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1590\/S0036-46651994000600009","article-title":"Usefulness of the detection of Toxoplasma gondii antigens in AIDS patients","volume":"36","author":"Fachado","year":"1994","journal-title":"Rev. Inst. Med. Trop. Sao Paulo"},{"key":"ref_100","first-page":"129","article-title":"Gu\u00eda de pr\u00e1ctica cl\u00ednica para toxoplasmosis durante el embarazo y toxoplasmosis cong\u00e9nita en Colombia","volume":"11","year":"2007","journal-title":"Infectio"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"2774","DOI":"10.1128\/iai.56.11.2774-2781.1988","article-title":"Damage of the outer membrane of enteric gram-negative bacteria by lactoferrin and transferrin","volume":"56","author":"Ellison","year":"1988","journal-title":"Infect. Immun."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1006\/expr.1995.1157","article-title":"Toxoplasma gondii: Parasiticidal Effects of Bovine Lactoferricin against Parasites","volume":"81","author":"Tanaka","year":"1995","journal-title":"Exp. Parasitol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/S0304-4017(96)01069-2","article-title":"Growth inhibitory effect of bovine lactoferrin on Toxoplasma gondii tachyzoites in murine macrophages: Role of radical oxygen and inorganic nitrogen oxide in Toxoplasma growth-inhibitory activity","volume":"68","author":"Tanaka","year":"1997","journal-title":"Vet. Parasitol."},{"key":"ref_104","first-page":"25","article-title":"Toxoplasma gondii: Inhibition of the intracellular growth by human lactoferrin","volume":"56","author":"Dzitko","year":"2007","journal-title":"Pol. J. Microbiol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1292\/jvms.58.61","article-title":"Growth Inhibitory Effects of Bovine Lactoferrin to Toxoplasma gondii Parasites in Murine Somatic Cells","volume":"58","author":"Tanaka","year":"1996","journal-title":"J. Vet. Med. Sci."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1292\/jvms.60.241","article-title":"Protective Effect of Lactoferricin against Toxoplasma gondii Infection in Mice","volume":"60","author":"Isamida","year":"1998","journal-title":"J. Vet. Med Sci."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1086\/526498","article-title":"Trichomonas vaginalis Infection: Can We Afford to Do Nothing?","volume":"197","author":"McClelland","year":"2008","journal-title":"J. Infect. Dis."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1128\/CMR.11.2.300","article-title":"Clinical and Microbiological Aspects of Trichomonas vaginalis","volume":"11","author":"Petrin","year":"1998","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1128\/CMR.17.4.794-803.2004","article-title":"Trichomoniasis","volume":"17","author":"Schwebke","year":"2004","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1084\/jem.160.2.398","article-title":"Iron uptake and increased intracellular enzyme activity follow host lactoferrin binding by Trichomonas vaginalis receptors","volume":"160","author":"Peterson","year":"1984","journal-title":"J. Exp. Med."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1111\/j.1365-2958.1992.tb00844.x","article-title":"Iron regulates growth of Trichomonas vaginalis and the expression of immunogenic trichomonad proteins","volume":"6","author":"Lehker","year":"1992","journal-title":"Mol. Microbiol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"3263","DOI":"10.1007\/s00436-021-07263-z","article-title":"Antitrichomonal activity of metronidazole-loaded lactoferrin nanoparticles in pigeon trichomoniasis","volume":"120","author":"Tabari","year":"2021","journal-title":"Parasitol. Res."},{"key":"ref_113","first-page":"537","article-title":"Effect of synthetic antimicrobial peptides on Naegleria fowleri trophozoites","volume":"45","author":"Tiewcharoen","year":"2014","journal-title":"Southeast Asian J. Trop. Med. Public Health"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.ijmm.2007.05.010","article-title":"Role of human tear fluid in Acanthamoeba interactions with the human corneal epithelial cells","volume":"298","author":"Alsam","year":"2008","journal-title":"Int. J. Med. Microbiol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1139\/bcb-2016-0054","article-title":"Effects of lactoferrin on the viability and the encystment of Acanthamoeba trophozoites","volume":"95","author":"Tomita","year":"2017","journal-title":"Biochem. Cell Biol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"254","DOI":"10.5604\/12321966.1233568","article-title":"Human infections caused by free-living amoebae","volume":"24","author":"Olender","year":"2017","journal-title":"Ann. Agric. Environ. Med."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1989","DOI":"10.1128\/JCM.02300-16","article-title":"Brain-Eating Amoebae: Predilection Sites in the Brain and Disease Outcome","volume":"55","author":"Ong","year":"2017","journal-title":"J. Clin. Microbiol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"781","DOI":"10.2217\/fmb-2016-0230","article-title":"Nf-GH, a glycosidase secreted by Naegleria fowleri, causes mucin degradation: An in vitro and in vivo study","volume":"12","author":"Arroyo","year":"2017","journal-title":"Future Microbiol."},{"key":"ref_119","first-page":"416712","article-title":"Iron-Binding Protein Degradation by Cysteine Proteases of Naegleria fowleri","volume":"2015","author":"Shibayama","year":"2015","journal-title":"BioMed Res. Int."},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"G\u00fc\u00e9mez, A., and Garc\u00eda, E. (2021). Primary Amoebic Meningoencephalitis by Naegleria fowleri: Pathogenesis and Treatments. Biomolecules, 11.","DOI":"10.3390\/biom11091320"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1016\/j.bbamem.2011.11.023","article-title":"Structural and biophysical characterization of an antimicrobial peptide chimera comprised of lactoferricin and lactoferrampin","volume":"1818","author":"Haney","year":"2012","journal-title":"Biochim. Biophys. Acta BBA-Biomembr."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1111\/j.1574-6976.2006.00023.x","article-title":"Acanthamoeba: Biology and increasing importance in human health","volume":"30","author":"Khan","year":"2006","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Fanselow, N., Sirajuddin, N., Yin, X.-T., Huang, A., and Stuart, P. (2021). Acanthamoeba keratitis, Pathology, Diagnosis and Treatment. Pathogens, 10.","DOI":"10.3390\/pathogens10030323"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/1756-3305-5-6","article-title":"Biology and pathogenesis of Acanthamoeba","volume":"5","author":"Siddiqui","year":"2012","journal-title":"Parasites Vectors"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1111\/jeu.12215","article-title":"Acanthamoeba castellanii Proteases are Capable of Degrading Iron-Binding Proteins as a Possible Mechanism of Pathogenicity","volume":"62","author":"Shibayama","year":"2015","journal-title":"J. Eukaryot. Microbiol."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/14\/8\/1702\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:08:55Z","timestamp":1760141335000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/14\/8\/1702"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,15]]},"references-count":125,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2022,8]]}},"alternative-id":["pharmaceutics14081702"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics14081702","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,15]]}}}