Abstract
Protozoal infections cause significant morbidity and mortality in humans and animals. The use of several antiprotozoal drugs is associated with serious adverse effects and resistance development, and drugs that are more effective are urgently needed. Microorganisms, mammalian cells and fluids, insects, and reptiles are sources of antimicrobial peptides (AMPs) that act against pathogenic microorganisms; these AMPs have been widely studied as a promising alternative therapeutic option to conventional antibiotics, aiming to treat infections caused by multidrug-resistant pathogens. One advantage of AMP molecules is their adaptability, as they can be easily fine-tuned for broad-spectrum or targeted activity by changing the amino acid residues in their sequence. Consequently, these variations in structural and physicochemical properties can alter the antimicrobial activities of AMPs and decrease resistance development. This article presents an overview of peptide activities against amebiasis, giardiasis, trichomoniasis, Chagas disease, leishmaniasis, malaria, and toxoplasmosis. AMPs and their analogs demonstrate great potential as therapeutics, with potent and selective activity, when compared with commercially available drugs, and hold the potential to act as new scaffolds for the development of novel anti-protozoal drugs.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Availability of data and materials
Data and materials information are available on request to the authors.
References
Abbassi F, Raja Z, Oury B, Gazanion E, Piesse C, Sereno D, Nicolas P, Foulon T, Ladram A (2013) Antibacterial and leishmanicidal activities of temporin-SHd, a 17-residue long membrane-damaging peptide. Biochimie 95:388–399. https://doi.org/10.1016/j.biochi.2012.10.015
Aguilar-Diaz H, Canizalez-Roman A, Nepomuceno-Mejia T, Gallardo-Vera F, Hornelas-Orozco Y, Nazmi K, Bolscher JGM, Carrero JC, Leon-Sicairos C, Leon-Sicairos N (2017) Parasiticidal effect of synthetic bovine lactoferrin peptides on the enteric parasite Giardia intestinalis. Biochem Cell Biol 95:82–90. https://doi.org/10.1139/bcb-2016-0079
Aley SB, Zimmerman M, Hetsko M, Selsted ME, Gillin FD (1994) Killing of Giardia lamblia by cryptdins and cationic neutrophil peptides. Infect Immun 62:5397–5403. https://doi.org/10.1128/iai.62.12.5397-5403
Amorim-Carmo B, Daniele-Silva A, Parente AMS, Furtado AA, Carvalho E, Oliveira JWF, Santos ECG, Silva MS, Silva SRB, Silva-Júnior AA, Monteiro NK, Fernandes-Pedrosa MF (2019) Potent and Broad-Spectrum Antimicrobial Activity of Analogs from the Scorpion Peptide Stigmurin. Int J Mol Sci 20:623. https://doi.org/10.3390/ijms20030623
André S, Raja Z, Humblot V, Piesse C, Foulon T, Sereno D, Oury B, Ladram A (2020) Functional characterization of temporin-she, a new broad-spectrum antibacterial and leishmanicidal temporin-sh paralog from the sahara frog (Pelophylax saharicus). Int J Mol Sci 21:1–19. https://doi.org/10.3390/ijms21186713
Aqeele G, Shayan P, Ebrahimzade Abkooh E, Mohebali M (2021) Evaluation of curcumin and CM11 peptide alone and in combination against amastigote form of Iranian strain of L. major (MRHO/IR75/ER) in vitro. Exp Parasitol 229:108151. https://doi.org/10.1016/j.exppara.2021.108151
Asadi A, Tavakoli Kareshk A, Sharifi I, Firouzeh N (2020) Murine cathelicidin: as a host defensive response against Leishmania major infection. J Parasit Dis 44:633–638. https://doi.org/10.1007/s12639-020-01238-0
Bandeira ICJ, Bandeira-Lima D, Mello CP, Pereira TP, De Menezes RRPPB, Sampaio TL, Falcão CB, Rádis-Baptista G, Martins AMC (2018) Antichagasic effect of crotalicidin, a cathelicidin-like vipericidin, found in Crotalus durissus terrificus rattlesnake’s venom gland. Parasitology 145:1059–1064. https://doi.org/10.1017/S0031182017001846
Barros GAC, Pereira AV, Barros LC, Lourenço A, Calvi SA, Santos LD, Barraviera B, Ferreira RS (2015) In vitro activity of phospholipase A2 and of peptides from Crotalus durissus terrificus venom against amastigote and promastigote forms of Leishmania (L.) infantum chagasi. J Venom Anim Toxins Incl Trop Dis 21:1–9. https://doi.org/10.1186/s40409-015-0049-0
Bérubé C, Gagnon D, Borgia A, Richard D, Voyer N (2019) Total synthesis and antimalarial activity of mortiamides A-D. Chem Commun 55:7434–7437. https://doi.org/10.1039/c9cc02864a
Bianchin A, Bell A, Chubb AJ, Doolan N, Leneghan D, Stavropoulos I, Shields DC, Mooney C (2015) Design and evaluation of antimalarial peptides derived from prediction of short linear motifs in proteins related to erythrocyte invasion. PLoS ONE 10:e0127383. https://doi.org/10.1371/journal.pone.0127383
Boparai JK, Sharma PK (2019) Mini review on antimicrobial peptides, sources, mechanism and recent applications. Protein Pep Lett 27:4–16. https://doi.org/10.2174/0929866526666190822165812
Burza S, Croft SL, Boelaert M (2018) Leishmaniasis. Lancet 392:951–970. https://doi.org/10.1016/S0140-6736(18)31204-2
Cabezas-Cruz A, Tonk M, Bouchut A, Pierrot C, Pierce RJ, Kotsyfakis M, Rahnamaeian M, Vilcinskas A, Khalife J, Valdés JJ (2016) Antiplasmodial activity is an ancient and conserved feature of tick defensins. Front Microbiol 7:1–12. https://doi.org/10.3389/fmicb.2016.01682
Campos-Salinas J, Cavazzuti A, O’Valle F, Forte-Lago I, Caro M, Beverley SM, Delgado M, Gonzalez-Rey E (2014) Therapeutic efficacy of stable analogues of vasoactive intestinal peptide against pathogens. J Biol Chem 289:14583–14599. https://doi.org/10.1074/jbc.M114.560573
Cao L, Jiang W, Cao S, Zhao P, Liu J, Dong H, Guo Y, Liu Q, Gong P (2019) In vitro leishmanicidal activity of antimicrobial peptide KDEL against Leishmania tarentolae. Acta Biochim Biophys Sin 51:1286–1292. https://doi.org/10.1093/abbs/gmz128
Carballar-Lejarazú R, Rodríguez MH, de La Cruz H-H, Ramos-Castañeda J, Possani LD, Zurita-Ortega M, Reynaud-Garza E, Hernández-Rivas R, Loukeris T, Lycett G, Lanz-Mendoza H (2008) Recombinant scorpine: a multifunctional antimicrobial peptide with activity against different pathogens. Cell Mol Life Sci 65:3081–3092. https://doi.org/10.1007/s00018-008-8250-8
Carrero JC, Reyes-López M, Serrano-luna J, Shibayama M (2019) International Journal of Medical Microbiology Intestinal amoebiasis: 160 years of its first detection and still remains as a health problem in developing countries. Int J Med Microbiol 310:151358. https://doi.org/10.1016/j.ijmm.2019.151358
CDC (2023a) Parasites - about parasites. https://www.cdc.gov/parasites/about.html. Accessed 23 June 2023
CDC (2023b) Parasites - toxoplasmosis (toxoplasma infection). https://www.cdc.gov/parasites/toxoplasmosis/biology.html. Accessed 27 June 2023
CDC (2023c) Parasites – chagas disease (American trypanosomiasis). https://www.cdc.gov/parasites/chagas/gen_info/detailed.html#intro. Accessed 30 June 2023
CDC (2023d) STD treatment guidelines. https://www.cdc.gov/std/tg2015/trichomoniasis.htm. Accessed 02 July 2023
CDC (2023e) Treatment of malaria (guidelines for clinicians). https://www.cdc.gov/malaria/diagnosis_treatment/clinicians1.html. Accessed 05 July 2023
CDC (2023f) Parasites - trichomoniasis (Trichomonas vaginalis). https://www.cdc.gov/dpdx/trichomoniasis/index.html. Accessed 09 July 2023
CDC (2023g) Parasites - amebiasis (Entamoeba histolytica infection). https://www.cdc.gov/parasites/amebiasis/pathogen.html. Accessed 17 July 2023
CDC (2023h) Parasites – malária (Plasmodium spp.). https://www.cdc.gov/dpdx/malaria/index.html. Accessed 20 July 2023
CDC (2023i) Parasites – giardiasis (Giardia lamblia). https://www.cdc.gov/parasites/giardia/index.html. Accessed 01 August 2023
Chen CH, Lu TK (2020) Development and challenges of antimicrobial peptides for therapeutic applications. Antibiotics 9:24. https://doi.org/10.3390/antibiotics9010024
Conroy T, Guo JT, Elias N, Cergol KM, Gut J, Legac J, Khatoon L, Liu Y, McGowan S, Rosenthal PJ, Hunt NH, Payne RJ (2014) Synthesis of gallinamide A analogues as potent falcipain inhibitors and antimalarials. J Med Chem 57:10557–10563. https://doi.org/10.1021/jm501439w
Costa NCS, Piccoli JP, Santos-Filho NA, Clementino LC, Fusco-Almeida AM, de Annunzio SR, Fontana CR, Verga JBM, Eto SF, Pizauro-Junior JM, Graminha MAS, Cilli EM (2020) Antimicrobial activity of RP-1 peptide conjugate with ferrocene group. PLoS ONE 15:e0228740. https://doi.org/10.1371/journal.pone.0228740
de Assis DRR, Pimentel PMO, dos Reis PVM, Rabelo RAN, Vitor RWA, Cordeiro MN, Felicori LF, Olórtegui CDC, Resende JM, Teixeira MM, Borges MH, de Lima ME, Pimenta AMC, Machado FS (2021) Tityus serrulatus (Scorpion): from the crude venom to the construction of synthetic peptides and their possible therapeutic application against Toxoplasma gondii infection. Front Cell Infect Microbiol 11:706618. https://doi.org/10.3389/fcimb.2021.706618
Dematei A, Nunes JB, Moreira DC, Jesus JA, Laurenti MD, Mengarda ACA, Vieira MS, do Amaral CP, Domingues MM, de Moraes J, Passero LFD, Brand G, Bessa LJ, Wimmer R, Kuckelhaus SAS, Tomás AM, Santos NC, Plácido A, Eaton P, Leite JRSA (2021) Mechanistic insights into the leishmanicidal and bactericidal activities of Batroxicidin, a cathelicidin-related peptide from a South American viper (Bothrops atrox). J Nat Prod 84:1787–1798. https://doi.org/10.1021/acs.jnatprod.1c00153
Díaz-Garrido P, Cárdenas-Guerra RE, Martínez I, Poggio S, Rodríguez-Hernández K, Rivera-Santiago L, Ortega-López J, Sánchez-Esquivel S, Espinoza B (2021) Differential activity on trypanosomatid parasites of a novel recombinant defensin type 1 from the insect Triatoma (Meccus) pallidipennis. Insect Biochem Mol Biol 139:103673. https://doi.org/10.1016/j.ibmb.2021.103673
Díaz-Godínez C, González-Galindo X, Meza-Menchaca T, Bobes RJ, de La Garza M, León-Sicairos N, Laclette JP, Carrero JC (2019) Synthetic bovine lactoferrin peptide Lfampin kills Entamoeba histolytica trophozoites by necrosis and resolves amoebic intracecal infection in mice. Biosci Rep 39:BSR20180850. https://doi.org/10.1042/BSR20180850
Dunay IR, Gajurel K, Dhakal R, Liesenfeld O, Montoya JG (2018) Treatment of toxoplasmosis: historical perspective, animal models, and current clinical practice. Clin Microbiol Rev 31:e00057-e117. https://doi.org/10.1128/CMR.00057-17
Einarsson E, Ma’ayeh S, Svärd SG (2016) An up-date on Giardia and giardiasis. Curr Opin Microbiol 34:47–52. https://doi.org/10.1016/j.mib.2016.07.019
Engels D, Zhou XN (2020) Neglected tropical diseases: an effective global response to local poverty-related disease priorities. Infect Dis Poverty 9:10. https://doi.org/10.1186/s40249-020-0630-9
Erfe MCB, David CV, Huang C, Lu V, Maretti-Mira AC, Haskell J, Bruhn KW, Yeaman MR, Craft N (2012) Efficacy of synthetic peptides RP-1 and AA-RP-1 against Leishmania species in vitro and in vivo. Antimicrob Agents Chemother 56:658–665. https://doi.org/10.1128/AAC.05349-11
Fagundez C, Sellanes D, Serra G (2018) Synthesis of cyclic peptides as potential anti-malarials. ACS Comb Sci 20:212–219. https://doi.org/10.1021/acscombsci.7b00154
Fathoni I, Petitbois JG, Alarif WM, Abdel-Lateff A, Al-Lihaibi SS, Yoshimura E, Nogata Y, Vairappan CS, Sholikhah EN, Okino T (2020) Bioactivities of Lyngbyabellins from Cyanobacteria of Moorea and Okeania Genera. Molecules 25:1–9. https://doi.org/10.3390/molecules25173986
Fieck A, Hurwitz I, Kang AS, Durvasula R (2010) Trypanosoma cruzi: Synergistic cytotoxicity of multiple amphipathic anti-microbial peptides to T. cruzi and potential bacterial hosts. Exp Parasitol 125:342–347. https://doi.org/10.1016/j.exppara.2010.02.016
Freire KA, Torres MDT, Lima DB, Monteiro ML, Bezerra de Menezes RRPP, Martins AMC, Oliveira VX (2020) Wasp venom peptide as a new antichagasic agent. Toxicon 181:71–78. https://doi.org/10.1016/j.toxicon.2020.04.099
Fujita Y, Seekaki P, Ogata N, Chiba K (2017) Physiological effects of a novel artificially synthesized antimalarial cyclic peptide: Mahafacyclin B. PLoS One 12:1–12. https://doi.org/10.1371/journal.pone.0188415
Garcia LS (2010) Malaria. Clin Lab Med 30:93–129. https://doi.org/10.1016/j.cll.2009.10.001
Ghorbani M, Farhoudi R (2018) Leishmaniasis in humans: drug or vaccine therapy? Drug Des Devel Ther 12:25–40. https://doi.org/10.2147/DDDT.S146521
Guerra MER, Fadel V, Maltarollo VG, Baldissera G, Honorio KM, Ruggiero JR, Dos Santos Cabrera MP (2017) MD simulations and multivariate studies for modeling the antileishmanial activity of peptides. Chem Biol Drug Des 4:501–510. https://doi.org/10.1111/cbdd.12970
Harder A, Greif G, Haberkorn A (2001) Chemotherapeutic approaches to protozoa: Giardia, Trichomonas and Entamoeba - current level of knowledge and outlook. Parasitol Res 87:785–786. https://doi.org/10.1007/s004360100405
Hayashi Y, Fukasawa W, Hirose T, Iwatsuki M, Hokari R, Ishiyama A, Kanaida M, Nonaka K, Také A, Otoguro K, Omura S, Shiomi K, Sunazuka T (2019) Kozupeptins, antimalarial agents produced by Paracamarosporium species: isolation, structural elucidation, total synthesis, and bioactivity. Org Lett 21:2180–2184. https://doi.org/10.1021/acs.orglett.9b00483
Hernandez-Flores JL, Rodriguez MC, Gastelum Arellanez A, Alvarez-Morales A, Avil EE (2015) Effect of recombinant prophenin 2 on the integrity and viability of Trichomonas vaginalis. BioMed Res Int 2015:430436. https://doi.org/10.1155/2015/430436
Huang HN, Chuang CM, Chen JY, Chieh-Yu P (2019) Epinecidin-1: A marine fish antimicrobial peptide with therapeutic potential against Trichomonas vaginalis infection in mice. Peptides 112:139–148. https://doi.org/10.1016/j.peptides.2018.12.004
Infante VV, Miranda-Olvera AD, De Leon-Rodriguez LM, Anaya-Velazquez F, Rodriguez MC, Avila EE (2011) Effect of the antimicrobial peptide tritrpticin on the in vitro viability and growth of Trichomonas vaginalis. Curr Microbiol 62:301–306. https://doi.org/10.1007/s00284-010-9709-z
Iwasaki K, Iwasaki A, Sumimoto S, Matsubara T, Sato T, Nozaki T, Saito-Nakano Y, Suenaga K (2020) Ikoamide, an Antimalarial Lipopeptide from an Okeania sp. Marine Cyanobacterium. J Nat Prod 83:481–488. https://doi.org/10.1021/acs.jnatprod.9b01147
Jang JP, Nogawa T, Futamura Y, Shimizu T, Hashizume D, Takahashi S, Jang JH, Ahn JS, Osada H (2017) Octaminomycins A and B, cyclic octadepsipeptides active against Plasmodium falciparum. J Nat Prod 80:134–140. https://doi.org/10.1021/acs.jnatprod.6b00758
Jokonya S, Langlais M, Leshabane M, Reader PW, Vosloo JA, Pfukwa R, Coertzen D, Birkholtz LM, Rautenbach M, Klumperman B (2020) Poly(N-vinylpyrrolidone) Antimalaria Conjugates of Membrane-Disruptive Peptides. Biomacromol 21:5053–5066. https://doi.org/10.1021/acs.biomac.0c01202
Kazuma K, Ando K, Nihei KI, Wang X, Rangel M, Franzolin MR, Mori-Yasumoto K, Sekita S, Kadowaki M, Satake M, Konno K (2017) Peptidomic analysis of the venom of the solitary bee Xylocopa appendiculata circumvolans. J Venom Anim Toxins Incl Trop Dis 23:1–11. https://doi.org/10.1186/s40409-017-0130-y
Khalili S, Mohebali M, Ebrahimzadeh E, Shayan P, Mohammadi-Yeganeh S, Moghaddam MM, Elikaee S, Akhoundi B, Sharifi-Yazdi MK (2018) Antimicrobial activity of an antimicrobial peptide against amastigote forms of Leishmania major. Vet Re Forum 9:323–328. https://doi.org/10.30466/vrf.2018.33107
Kissinger P (2015) Trichomonas vaginalis: A review of epidemiologic, clinical and treatment issues. BMC Inf Dis 15:1–8. https://doi.org/10.1186/s12879-015-1055-0
Konno K, Kazuma K, Rangel M, Stolarz-De-oliveira J, Fontana R, Kawano M, Fuchino H, Hide I, Yasuhara T, Nakata Y (2019) New mastoparan peptides in the venom of the solitary eumenine wasp Eumenes micado. Toxins 11:1–15. https://doi.org/10.3390/toxins11030155
Kückelhaus SAS, de Aquino DS, Borges TK, Moreira DC, Leite LM, Muniz-Junqueira MI, Kückelhaus CS, Sierra Romero GA, Prates MV, Bloch C, Leite JRSA (2020) Phylloseptin-1 is leishmanicidal for amastigotes of Leishmania amazonensis inside infected macrophages. Int J Env Res Public Health 17:1–14. https://doi.org/10.3390/ijerph17134856
Kumar V, Chugh A (2021) Peptide-mediated leishmaniasis management strategy: Tachyplesin emerges as an effective anti-leishmanial peptide against Leishmania donovani. Biochim Biophys Acta Biomembr 1863:183629. https://doi.org/10.1016/j.bbamem.2021.183629
Kumar P, Kizhakkedathu JN, Straus SK (2018) Antimicrobial peptides: Diversity, mechanism of action and strategies to improve the activity and biocompatibility in vivo. Biomolecules 8:4. https://doi.org/10.3390/biom8010004
León-Sicairos N, Reyes-López M, Ordaz-Pichardo C, De La Garza M (2006) Microbicidal action of lactoferrin and lactoferricin and their synergistic effect with metronidazole in Entamoeba histolytica. Biochem Cell Biol 84:327–336. https://doi.org/10.1139/O06-060
Lin MC, Hui CF, Chen JY, Wu JL (2012) The antimicrobial peptide, shrimp anti-lipopolysaccharide factor (SALF), inhibits proinflammatory cytokine expressions through the MAPK and NF-κB pathways in Trichomonas vaginalis adherent to HeLa cells. Peptides 38:197–207. https://doi.org/10.1016/j.peptides.2012.10.003
Liu R, Ni Y, Song J, Xu Z, Qiu J, Wang L, Zhu Y, Huang Y, Ji M, Chen Y (2019) Research on the effect and mechanism of antimicrobial peptides HPRP- A1/A2 work against Toxoplasma gondii infection. Parasite Immunol 41:1–10. https://doi.org/10.1111/pim.12619
Lourido S (2019) Toxoplasma gondii. Trends in Parasitol 35:944–945. https://doi.org/10.1016/j.pt.2019.07.001
Lynn MA, Kindrachuk J, Marr AK, Jenssen H, Panté N, Elliott MR, Napper S, Hancock RE, McMaster WR (2011) Effect of BMAP-28 antimicrobial peptides on Leishmania major promastigote and amastigote growth: Role of leishmanolysin in parasite survival. PLoS Negl Trop Dis 5:e1141. https://doi.org/10.1371/journal.pntd.0001141
Mahdavi Abhari F, Pirestani M, Dalimi A (2019) Anti-amoebic activity of a cecropin-melittin hybrid peptide (CM11) against trophozoites of Entamoeba histolytica. Wien Klin Wochenschr 131:427–434. https://doi.org/10.1007/s00508-019-01540-9
Marr AK, Cen S, Hancock REW, McMaster WR (2016) Identification of synthetic and natural host defense peptides with leishmanicidal activity. Antimicrob Agents Chemother 60:2484–2491. https://doi.org/10.1128/AAC.02328-15
Mello CP, Lima DB, Menezes RRPPB, Bandeira ICJ, Tessarolo LD, Sampaio TL, Falcão CB, Rádis-Baptista G, Martins AMC (2017) Evaluation of the antichagasic activity of batroxicidin, a cathelicidin-related antimicrobial peptide found in Bothrops atrox venom gland. Toxicon 130:56–62. https://doi.org/10.1016/j.toxicon.2017.02.031
Mendes B, Almeida JR, Vale N, Gomes P, Gadelha FR, da Silva SL, Miguel DC (2019) Potential use of 13-mer peptides based on phospholipase and oligoarginine as leishmanicidal agents. Comp Biochem Physiol C Toxicol Pharmacol 226:108612. https://doi.org/10.1016/j.cbpc.2019.108612
Mohammed SEA, Kabashi AS, Koko WS, Azim MK (2015) Antigiardial activity of glycoproteins and glycopeptides from Ziziphus honey. Nat Prod Res 29:2100–2102. https://doi.org/10.1080/14786419.2014.986659
Monteiro ML, Lima DB, Menezes RRPPB, Sampaio TL, Silva BP, Serra Nunes JV, Cavalcanti MM, Morlighem JE, Martins AMC (2020) Antichagasic effect of hemocyanin derived from antimicrobial peptides of Penaeus monodon shrimp. Exp Parasitol 215:107930. https://doi.org/10.1016/j.exppara.2020.107930
Mutwiri GK, Henk WG, Enright FM, Corbeil LB (2000) Effect of the antimicrobial peptide, D-hecate, on Trichomonads. J Parasitol 86:1355–1359. https://doi.org/10.1645/0022-3395(2000)086[1355:eotapd]2.0.co;2
Pan CY, Chen JY, Lin TL, Lin CH (2009) In vitro activities of three synthetic peptides derived from epinecidin-1 and an anti-lipopolysaccharide factor against Propionibacterium acnes, Candida albicans, and Trichomonas vaginalis. Peptides 30:1058–1068. https://doi.org/10.1016/j.peptides.2009.02.006
Patiño-Márquez IA, Manrique-Moreno M, Patiño-González E, Jemioła-Rzemińska M, Strzałka K (2018a) Effect of antimicrobial peptides from Galleria mellonella on molecular models of Leishmania membrane. Thermotropic and fluorescence anisotropy study. J Antibiot 71:642–652. https://doi.org/10.1038/s41429-018-0050-2
Patiño-Márquez IA, Patiño-González E, Hernández-Villa L, Ortíz-Reyes B, Manrique-Moreno M (2018b) Identification and evaluation of Galleria mellonella peptides with antileishmanial activity. Anal Biochem 546:35–42. https://doi.org/10.1016/j.ab.2018.01.029
Pedron CN, Freire KA, Torres MDT, Lima DB, Monteiro ML, Menezes RRPPB, Martins AMC, Oliveira VX (2020) Arg-substituted VmCT1 analogs reveals promising candidate for the development of new antichagasic agent. Parasitology 147:1810–1818. https://doi.org/10.1017/S0031182020001882
Pedron CN, Silva AF, Torres MDT, Oliveira CS, Andrade GP, Cerchiaro G, Pinhal MAS, de la Fuente-Nunez C, Oliveira Junior VX (2021) Net charge tuning modulates the antiplasmodial and anticancer properties of peptides derived from scorpion venom. J Pept Sci 27:e3296. https://doi.org/10.1002/psc.3296
Peña-Carrillo MS, Pinos-Tamayo EA, Mendes B, Domínguez-Borbor C, Proaño-Bolaños C, Miguel DC, Almeida JR (2021) Dissection of phospholipases A2 reveals multifaceted peptides targeting cancer cells, Leishmania and bacteria. Bioorg Chem 114:105041. https://doi.org/10.1016/j.bioorg.2021.105041
Pérez-Cordero JJ, Lozano JM, Cortés J, Delgado G (2011) Leishmanicidal activity of synthetic antimicrobial peptides in an infection model with human dendritic cells. Peptides 32:683–690. https://doi.org/10.1016/j.peptides.2011.01.011
Pinto EG, Pimenta DC, Antoniazzi MM, Jared C, Tempone AG (2013) Antimicrobial peptides isolated from Phyllomedusa nordestina (Amphibia) alter the permeability of plasma membrane of Leishmania and Trypanosoma cruzi. Exp Parasitol 135:655–660. https://doi.org/10.1016/j.exppara.2013.09.016
Pitale DM, Kaur G, Baghel M, Kaur KJ, Shaha C (2020) Halictine-2 antimicrobial peptide shows promising anti-parasitic activity against Leishmania spp. Exp Parasitol 218:107987. https://doi.org/10.1016/j.exppara.2020.107987
Preet S, Bharati S, Shukla G, Koul A, Rishi P (2011) Evaluation of amoebicidal potential of paneth cell cryptdin-2 against Entamoeba histolytica. PLoS Negl Trop Dis 5:e1386. https://doi.org/10.1371/journal.pntd.0001386
Pretzel J, Mohring F, Rahlfs S, Becker K (2013) Antiparasitic peptides. Adv Biochem Eng Biotechnol 135:157–192. https://doi.org/10.1007/10_2013_191
Raja Z, Andrea S, Abbassi F, Humblot V, Lequin O, Bouceba T, Correia I, Casale S, Foulon T, Sereno D, Oury B, Ladram A (2017) Insight into the mechanism of action of temporin-SHa, a new broad-spectrum antiparasitic and antibacterial agent. PLoS One 12:e0174024. https://doi.org/10.1371/journal.pone.0174024
Rangel M, dos Santos Cabrera MP, Kazuma K, Ando K, Wang X, Kato M, Nihei K, Hirata IY, Cross TJ, Garcia AN, Faquim-Mauro EL, Franzolin MR, Fuchino H, Mori-Yasumoto K, Sekita S, Kadowaki M, Satake M, Konno K (2011) Chemical and biological characterization of four new linear cationic α-helical peptides from the venoms of two solitary eumenine wasps. Toxicon 57:1081–1092. https://doi.org/10.1016/j.toxicon.2011.04.014
Rigo GV, Frank LA, Galego GB, Santos ALSd, Tasca T (2022) Novel treatment approaches to combat trichomoniasis, a neglected and sexually transmitted infection caused by Trichomonas vaginalis: translational perspectives. Venereology 1:47–80. https://doi.org/10.3390/venereology1010005
Robledo SM, Pérez-Silanes S, Fernández-Rubio C, Poveda A, Monzote L, González VM, Alonso-Collado P, Carrión J (2023) Neglected zoonotic diseases: advances in the development of cell-penetrating and antimicrobial peptides against leishmaniosis and chagas disease. Pathogens 12:939. https://doi.org/10.3390/pathogens12070939
Ruiz-Santaquiteria M, Sánchez-Murcia PA, Toro MA, de Lucio H, Gutiérrez KJ, de Castro S, Carneiro FAC, Gago F, Jiménez-Ruiz A, Camarasa MJ, Velázquez S (2017) First example of peptides targeting the dimer interface of Leishmania infantum trypanothione reductase with potent in vitro antileishmanial activity. Eur J Med Chem 135:49–59. https://doi.org/10.1016/j.ejmech.2017.04.020
Savoia D, Donalisio M, Civra A, Salvadori S, Guerrini R (2010) In vitro activity of dermaseptin S1 derivatives against genital pathogens. APMIS 118:674–680. https://doi.org/10.1111/j.1600-0463.2010.02637.x
Silva T, Abengózar MA, Fernandez-Reyes M, Andreu D, Nazmi K, Bolscher JGM, Bastos M, Rivas L (2012) Enhanced leishmanicidal activity of cryptopeptide chimeras from the active N1 domain of bovine lactoferrin. Amino Acids 43:2265–2277. https://doi.org/10.1007/s00726-012-1304-0
Silva AF, Torres MDT, Silva LDS, Alves FL, Pinheiro AADS, Miranda A, Capurro ML, Oliveira VX (2015) New linear antiplasmodial peptides related to angiotensin II. Malaria J 14:1–10. https://doi.org/10.1186/s12936-015-0974-y
Silva AF, Torres MDT, Silva LS, Alves FL, De Sá Pinheiro AA, Miranda A, Capurro ML, De La Fuente-Nunez C, Oliveira VX (2017) Angiotensin II-derived constrained peptides with antiplasmodial activity and suppressed vasoconstriction. Sci Rep 7:14326. https://doi.org/10.1038/s41598-017-14642-z
Söbirk SK, Mörgelin M, Egesten A, Bates P, Shannon O, Collin M (2013) Human chemokines as antimicrobial peptides with direct parasiticidal effect on Leishmania mexicana in vitro. PLoS ONE 8:e58129. https://doi.org/10.1371/journal.pone.0058129
Stanley SL (2003) Amoebiasis. Lancet 361:1025–1034. https://doi.org/10.1016/S0140-6736(03)12830-9
Stoye A, Juillard A, Tang AH, Legac J, Gut J, White KL, Charman SA, Rosenthal PJ, Grau GER, Hunt NH, Payne RJ (2019) Falcipain inhibitors based on the natural product Gallinamide A are potent in vitro and in vivo antimalarials. J Med Chem 62:5562–5578. https://doi.org/10.1021/acs.jmedchem.9b00504
Sweeney-Jones AM, Gagaring K, Antonova-Koch J, Zhou H, Mojib N, Soapi K, Skolnick J, McNamara CW, Kubanek J (2020) Antimalarial peptide and polyketide natural products from the Fijian marine cyanobacterium Moorea producens. Mar Drugs 18:167. https://doi.org/10.3390/md18030167
Tanaka T, Rahman MM, Battur B, Boldbaatar D, Liao M, Umemiya-Shirafuji R, Xuan X, Fujisaki K (2010) Parasiticidal activity of human α-defensin-5 against Toxoplasma gondii. In Vitro Cell Dev Biol - Anim 46(6):560–565. https://doi.org/10.1007/s11626-009-9271-9
Tanaka T, Maeda H, Matsuo T, Boldbattar D, Umemiya-Shirafuji R, Kume A, Suzuki H, Xuan X, Tsuji N, Fujisaki K (2012) Parasiticidal activity of Haemaphysalis longicornis longicin P4 peptide against Toxoplasma gondii. Peptides 34:242–250. https://doi.org/10.1016/j.peptides.2011.07.027
Tang Y, Hou S, Li X, Wu M, Ma B, Wang Z, Jiang J, Deng M, Duan Z, Tang X, Liu Y, Wang W, Han X, Jiang L (2019) Anti-parasitic effect on Toxoplasma gondii induced by a spider peptide lycosin-I. Exp Parasitol 198:17–25. https://doi.org/10.1016/j.exppara.2019.01.009
Tonk M, Pierrot C, Cabezas-Cruz A, Rahnamaeian M, Khalife J, Vilcinskas A (2019) The Drosophila melanogaster antimicrobial peptides Mtk-1 and Mtk-2 are active against the malarial parasite Plasmodium falciparum. Parasitol Res 118:1993–1998. https://doi.org/10.1007/s00436-019-06305-x
Torres MDT, Silva AF, Alves FL, Capurro ML, Miranda A, Vani Xavier O (2015) Highly potential antiplasmodial restricted peptides. Chem Biol Drug Des 85:163–171. https://doi.org/10.1111/cbdd.12354
Torres MDT, Silva AF, Andrade GP, Pedron CN, Cerchiaro G, Ribeiro AO, Oliveira VX (2020) de la Fuente-Nunez C (2020) The wasp venom antimicrobial peptide polybia-CP and its synthetic derivatives display antiplasmodial and anticancer properties. Bioeng Transl Med 5:e10167. https://doi.org/10.1002/btm2.10167
Turchany JM, Aley SB, Gillin FD (1995) Giardicidal activity of lactoferrin and N-terminal peptides. Inf Imm 63:4550–4552. https://doi.org/10.1128/iai.63.11.4550-4552.1995
Vale N, Aguiar L, Gomes P (2014) Antimicrobial peptides: a new class of antimalarial drugs? Front Pharmacol 5:275. https://doi.org/10.3389/fphar.2014.00275
Vinhote JFC, Lima DB, Menezes RRPPB, Mello CP, de Souza BM, Havt A, Palma MS, Santos RP, Albuquerque EL, Freire VN, Martins AMC (2017) Trypanocidal activity of mastoparan from Polybia paulista wasp venom by interaction with TcGAPDH. Toxicon 137:168–172. https://doi.org/10.1016/j.toxicon.2017.08.002
Watkins RR, Eckmann L (2014) Treatment of giardiasis: Current status and future directions topical collection on intra-abdominal infections, hepatitis, and gastroenteritis. Curr Infect Dis Rep 16:396. https://doi.org/10.1007/s11908-014-0396-y
WHO (2018) https://www.who.int/teams/control-of-neglected-tropical-diseases/overview
WHO (2021) World malaria report 2021. Geneva: World Health Organization. Licence: CCBY-NC-SA 3.0 IGO
WHO (2023a) https://www.who.int/news/item/19-10-2021-scientists-share-data-from-first-who-recommended-malaria-vaccine. Accessed 2 Aug 2023
WHO (2023b) https://www.who.int/news-room/fact-sheets/detail/leishmaniasis. Accessed 2 Aug 2023
Yu Y, Zhao P, Cao L, Gong P, Yuan S, Yao X, Guo Y, Dong H, Jiang W (2020) A novel anti-microbial peptide from pseudomonas, redlk induced growth inhibition of Leishmania tarentolae promastigote in vitro. Korean J Parasitol 58:173–179. https://doi.org/10.3347/kjp.2020.58.2.173
Zahedifard F, Lee H, No JH, Salimi M, Seyed N, Asoodeh A, Rafati S (2020) Comparative study of different forms of Jellein antimicrobial peptide on Leishmania parasite. Exp Parasitol 209:107823. https://doi.org/10.1016/j.exppara.2019.107823
Zasloff M (2002) Innate immunity, antimicrobial peptides, and protection of the oral cavity. Lancet 360:1116–1117. https://doi.org/10.1016/S0140-6736(02)11239-6
Zhang XC, Zhang F (2018) Chapter Four - The potential control strategies based on the interaction between indoor cockroaches and their symbionts in China. In: Smagghe G (ed) Advances in insect physiology. Academic Press, 55. pp 55–122. https://doi.org/10.1016/bs.aiip.2018.07.001
Acknowledgements
The authors thank the native-English-speaking scientist Nicola Amanda Conran Zorzetto for the English language revision.
Funding
This study was supported by the Brazilian agencies Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) – Programa de Pós-Graduação em Ciências Farmacêuticas, and Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS). A.J.M. (grant 304606/2022–7) and T.T. (grant 09764/2021–1) thank CNPq for researcher fellowships.
Author information
Authors and Affiliations
Contributions
C.L.H. and T.T. conceptualized the idea of the review; C.L.H. searched the literature and wrote the manuscript draft; A.J.M. performed the peptide structures analysis; C.L.H. designed the figures and organized the tables. A.J.M. and T.T. revised the manuscript.
Corresponding author
Ethics declarations
Ethical approval
Not applicable.
Competing interests
The authors declare no competing interests.
Additional information
Section Editor: Dietmar Steverding
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Hagemann, C.L., Macedo, A.J. & Tasca, T. Therapeutic potential of antimicrobial peptides against pathogenic protozoa. Parasitol Res 123, 122 (2024). https://doi.org/10.1007/s00436-024-08133-0
Received:
Accepted:
Published:
DOI: https://doi.org/10.1007/s00436-024-08133-0