{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T15:55:48Z","timestamp":1764172548690,"version":"build-2065373602"},"reference-count":118,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,12,8]],"date-time":"2022-12-08T00:00:00Z","timestamp":1670457600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"FCT - Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["PTDC\/CVT-CVT\/6798\/2020","SFRH\/BD\/140119\/2018","SFRH\/BD\/140177\/2018","2021.04285.CEECIND"],"award-info":[{"award-number":["PTDC\/CVT-CVT\/6798\/2020","SFRH\/BD\/140119\/2018","SFRH\/BD\/140177\/2018","2021.04285.CEECIND"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"name":"FCT individual fellowships","award":["PTDC\/CVT-CVT\/6798\/2020","SFRH\/BD\/140119\/2018","SFRH\/BD\/140177\/2018","2021.04285.CEECIND"],"award-info":[{"award-number":["PTDC\/CVT-CVT\/6798\/2020","SFRH\/BD\/140119\/2018","SFRH\/BD\/140177\/2018","2021.04285.CEECIND"]}]},{"name":"European Social Fund","award":["PTDC\/CVT-CVT\/6798\/2020","SFRH\/BD\/140119\/2018","SFRH\/BD\/140177\/2018","2021.04285.CEECIND"],"award-info":[{"award-number":["PTDC\/CVT-CVT\/6798\/2020","SFRH\/BD\/140119\/2018","SFRH\/BD\/140177\/2018","2021.04285.CEECIND"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Leishmaniasis, a vector-borne parasitic protozoan disease, is among the most important neglected tropical diseases. In the absence of vaccines, disease management is challenging. The available chemotherapy is suboptimal, and there are growing concerns about the emergence of drug resistance. Thus, a better understanding of parasite biology is essential to generate new strategies for disease control. In this context, in vitro parasite exoproteome characterization enabled the identification of proteins involved in parasite survival, pathogenesis, and other biologically relevant processes. After 2005, with the availability of genomic information, these studies became increasingly feasible and revealed the true complexity of the parasite exoproteome. After the discovery of Leishmania extracellular vesicles (EVs), most exoproteome studies shifted to the characterization of EVs. The non-EV portion of the exoproteome, named the vesicle-depleted exoproteome (VDE), has been mostly ignored even if it accounts for a significant portion of the total exoproteome proteins. Herein, we summarize the importance of total exoproteome studies followed by a special emphasis on the available information and the biological relevance of the VDE. Finally, we report on how VDE can be studied and disclose how it might contribute to providing biologically relevant targets for diagnosis, drug, and vaccine development.<\/jats:p>","DOI":"10.3390\/microorganisms10122435","type":"journal-article","created":{"date-parts":[[2022,12,9]],"date-time":"2022-12-09T02:20:31Z","timestamp":1670552431000},"page":"2435","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Leishmania Vesicle-Depleted Exoproteome: What, Why, and How?"],"prefix":"10.3390","volume":"10","author":[{"given":"Sofia","family":"Esteves","sequence":"first","affiliation":[{"name":"Laboratory of Microbiology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"},{"name":"Institute for Research and Innovation in Health (i3S), University of Porto, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6299-8417","authenticated-orcid":false,"given":"In\u00eas","family":"Costa","sequence":"additional","affiliation":[{"name":"Laboratory of Microbiology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"},{"name":"Institute for Research and Innovation in Health (i3S), University of Porto, 4200-135 Porto, Portugal"}]},{"given":"Sara","family":"Luelmo","sequence":"additional","affiliation":[{"name":"Institute for Research and Innovation in Health (i3S), University of Porto, 4200-135 Porto, Portugal"}]},{"given":"Nuno","family":"Santar\u00e9m","sequence":"additional","affiliation":[{"name":"Laboratory of Microbiology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"},{"name":"Institute for Research and Innovation in Health (i3S), University of Porto, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2392-6087","authenticated-orcid":false,"given":"Anabela","family":"Cordeiro-da-Silva","sequence":"additional","affiliation":[{"name":"Laboratory of Microbiology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"},{"name":"Institute for Research and Innovation in Health (i3S), University of Porto, 4200-135 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,8]]},"reference":[{"key":"ref_1","unstructured":"WHO (2022, October 02). Leishmaniasis, Available online: http:\/\/www.who.int\/leishmaniasis\/en\/."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Vuitika, L., Prates-Syed, W.A., Silva, J.D.Q., Crema, K.P., Cortes, N., Lira, A., Lima, J.B.M., Camara, N.O.S., Schimke, L.F., and Cabral-Marques, O. (2022). Vaccines against Emerging and Neglected Infectious Diseases: An Overview. Vaccines, 10.","DOI":"10.3390\/vaccines10091385"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1039\/D1MD00362C","article-title":"Current leishmaniasis drug discovery","volume":"13","author":"Pinheiro","year":"2022","journal-title":"RSC Med. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s13071-021-05129-y","article-title":"Identification of asymptomatic Leishmania infections: A scoping review","volume":"15","author":"Corbeil","year":"2022","journal-title":"Parasit Vectors"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3201\/eid2512.190164","article-title":"Canine Leishmaniasis Control in the Context of One Health","volume":"25","author":"Miro","year":"2019","journal-title":"Emerg. Infect. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1586\/epr.12.52","article-title":"Exoproteomics: Exploring the world around biological systems","volume":"9","author":"Armengaud","year":"2012","journal-title":"Expert Rev. Proteom."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1016\/j.bbapap.2018.05.011","article-title":"Proteomic approaches unravel the intricacy of secreted proteins of Leishmania: An updated review","volume":"1866","author":"Garg","year":"2018","journal-title":"Biochim. Biophys. Acta Proteins Proteom."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1242\/jcs.056465","article-title":"An exosome-based secretion pathway is responsible for protein export from Leishmania and communication with macrophages","volume":"123","author":"Silverman","year":"2010","journal-title":"J. Cell Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"100","DOI":"10.3389\/fcimb.2019.00100","article-title":"Modulation of Host-Pathogen Communication by Extracellular Vesicles (EVs) of the Protozoan Parasite Leishmania","volume":"9","author":"Dong","year":"2019","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.molimm.2021.04.003","article-title":"Extracellular vesicles and leishmaniasis: Current knowledge and promising avenues for future development","volume":"135","author":"Dong","year":"2021","journal-title":"Mol. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"602502","DOI":"10.3389\/fcimb.2020.602502","article-title":"Extracellular Vesicles in Trypanosomatids: Host Cell Communication","volume":"10","author":"Torrecilhas","year":"2020","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.mib.2016.04.008","article-title":"Emerging roles for extracellular vesicles in parasitic infections","volume":"32","author":"Marti","year":"2016","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.molimm.2021.01.008","article-title":"Extracellular Vesicles during TriTryps infection: Complexity and future challenges","volume":"132","author":"Rossi","year":"2021","journal-title":"Mol. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.1017\/S0031182018001105","article-title":"A new landscape of host-protozoa interactions involving the extracellular vesicles world","volume":"145","author":"Gavinho","year":"2018","journal-title":"Parasitology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1038\/nrmicro.2016.110","article-title":"Sending a message: Extracellular vesicles of pathogenic protozoan parasites","volume":"14","author":"Szempruch","year":"2016","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2005","DOI":"10.1007\/s00436-020-06691-7","article-title":"Membrane-bound extracellular vesicles secreted by parasitic protozoa: Cellular structures involved in the communication between cells","volume":"119","author":"Barrias","year":"2020","journal-title":"Parasitol. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"559","DOI":"10.2217\/fmb-2019-0087","article-title":"Leishmania and its exosomal pathway: A novel direction for vaccine development","volume":"14","author":"Olivier","year":"2019","journal-title":"Future Microbiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"27066","DOI":"10.3402\/jev.v4.27066","article-title":"Biological properties of extracellular vesicles and their physiological functions","volume":"4","author":"Siljander","year":"2015","journal-title":"J. Extracell. Vesicles"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2653","DOI":"10.1016\/j.bbapap.2013.09.015","article-title":"Comparative analysis of Leishmania exoproteomes: Implication for host-pathogen interactions","volume":"1834","author":"Peysselon","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1016\/j.dib.2018.11.147","article-title":"Proteome profiling of secreted and membrane vesicle associated proteins of an invasive and a commensal Staphylococcus haemolyticus isolate","volume":"22","author":"Cavanagh","year":"2019","journal-title":"Data Brief"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4207","DOI":"10.1021\/acs.jproteome.5b00312","article-title":"Proteome Profiles of Outer Membrane Vesicles and Extracellular Matrix of Pseudomonas aeruginosa Biofilms","volume":"14","author":"Couto","year":"2015","journal-title":"J. Proteome Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.jprot.2013.03.012","article-title":"Exoproteome dynamics in Leishmania infantum","volume":"84","author":"Santarem","year":"2013","journal-title":"J. Proteom."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1016\/j.jprot.2015.06.009","article-title":"Quantitative proteomics unravels that the post-transcriptional regulator Crc modulates the generation of vesicles and secreted virulence determinants of Pseudomonas aeruginosa","volume":"127","author":"Corona","year":"2015","journal-title":"J. Proteom."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4270","DOI":"10.1021\/acs.jproteome.5b00411","article-title":"Global Proteomic Profiling of the Secretome of Candida albicans ecm33 Cell Wall Mutant Reveals the Involvement of Ecm33 in Sap2 Secretion","volume":"14","author":"Monteoliva","year":"2015","journal-title":"J. Proteome Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1463779","DOI":"10.1080\/20013078.2018.1463779","article-title":"Proteomic analysis reveals different composition of extracellular vesicles released by two Trypanosoma cruzi strains associated with their distinct interaction with host cells","volume":"7","author":"Ribeiro","year":"2018","journal-title":"J. Extracell. Vesicles"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1080\/21505594.2018.1451184","article-title":"Extracellular vesicles and vesicle-free secretome of the protozoa Acanthamoeba castellanii under homeostasis and nutritional stress and their damaging potential to host cells","volume":"9","author":"Goncalves","year":"2018","journal-title":"Virulence"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1186\/s13071-022-05364-x","article-title":"Eimeria falciformis secretes extracellular vesicles to modulate proinflammatory response during interaction with mouse intestinal epithelial cells","volume":"15","author":"Olajide","year":"2022","journal-title":"Parasit Vectors"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1021\/pr300947g","article-title":"Proteomic analysis of Trypanosoma cruzi secretome: Characterization of two populations of extracellular vesicles and soluble proteins","volume":"12","author":"Rodrigues","year":"2013","journal-title":"J. Proteome Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"960909","DOI":"10.3389\/fimmu.2022.960909","article-title":"Comparison of EV-free fraction, EVs, and total secretome of amniotic mesenchymal stromal cells for their immunomodulatory potential: A translational perspective","volume":"13","author":"Papait","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1586\/14789450.4.2.239","article-title":"Approaches to the study of the cell secretome","volume":"4","author":"Hathout","year":"2007","journal-title":"Expert Rev. Proteom."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1111\/j.1574-695X.2009.00608.x","article-title":"Deciphering the Leishmania exoproteome: What we know and what we can learn","volume":"58","author":"Corrales","year":"2010","journal-title":"FEMS Immunol. Med. Microbiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1126\/science.271.5255.1519","article-title":"Common principles of protein translocation across membranes","volume":"271","author":"Schatz","year":"1996","journal-title":"Science"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1128\/MMBR.66.1.122-154.2002","article-title":"Secretory pathway of trypanosomatid parasites","volume":"66","author":"McConville","year":"2002","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1111\/j.1600-0854.2007.00558.x","article-title":"Intracellular trafficking in the trypanosomatids","volume":"8","author":"Field","year":"2007","journal-title":"Traffic"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0166-6851(01)00262-6","article-title":"The flagellum and flagellar pocket of trypanosomatids","volume":"115","author":"Landfear","year":"2001","journal-title":"Mol. Biochem. Parasitol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1111\/j.1550-7408.1987.tb03216.x","article-title":"Receptor-mediated endocytosis in the bloodstream form of Trypanosoma brucei","volume":"34","author":"Coppens","year":"1987","journal-title":"J. Protozool."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/S0962-8924(97)10046-0","article-title":"Endocytosis and secretion in trypanosomatid parasites\u2014Tumultuous traffic in a pocket","volume":"7","author":"Overath","year":"1997","journal-title":"Trends Cell Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1083\/jcb.106.1.77","article-title":"Intracellular transport of a variant surface glycoprotein in Trypanosoma brucei","volume":"106","author":"Duszenko","year":"1988","journal-title":"J. Cell Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1017\/S0031182002001439","article-title":"The role of promastigote secretory gel in the origin and transmission of the infective stage of Leishmania mexicana by the sandfly Lutzomyia longipalpis","volume":"124","author":"Rogers","year":"2002","journal-title":"Parasitology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1038\/nature02675","article-title":"Transmission of cutaneous leishmaniasis by sand flies is enhanced by regurgitation of fPPG","volume":"430","author":"Rogers","year":"2004","journal-title":"Nature"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Rogers, M.E., and Bates, P.A. (2007). Leishmania manipulation of sand fly feeding behavior results in enhanced transmission. PLoS Pathog., 3.","DOI":"10.1371\/journal.ppat.0030091"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1111\/j.1462-5822.2010.01439.x","article-title":"Proteophosphoglycan confers resistance of Leishmania major to midgut digestive enzymes induced by blood feeding in vector sand flies","volume":"12","author":"Secundino","year":"2010","journal-title":"Cell. Microbiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1016\/j.micinf.2010.05.014","article-title":"Leishmania infantum proteophosphoglycans regurgitated by the bite of its natural sand fly vector, Lutzomyia longipalpis, promote parasite establishment in mouse skin and skin-distant tissues","volume":"12","author":"Rogers","year":"2010","journal-title":"Microbes Infect."},{"key":"ref_44","first-page":"76","article-title":"Identification and partial characterization of an extracellular acid phosphatase activity of Leishmania donovani promastigotes","volume":"2","author":"Gottlieb","year":"1982","journal-title":"Mol. Cell. Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1111\/j.1574-6968.1992.tb05322.x","article-title":"Acid phosphatase activity of promastigotes of Leishmania donovani: A marker of virulence","volume":"73","author":"Singla","year":"1992","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2856","DOI":"10.1128\/iai.56.11.2856-2860.1988","article-title":"Acid phosphatase activity of virulent and avirulent clones of Leishmania donovani promastigotes","volume":"56","author":"Katakura","year":"1988","journal-title":"Infect. Immun."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"8774","DOI":"10.1073\/pnas.88.19.8774","article-title":"Secreted acid phosphatase of Leishmania mexicana: A filamentous phosphoglycoprotein polymer","volume":"88","author":"Ilg","year":"1991","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1111\/j.1550-7408.2004.tb00171.x","article-title":"The human pathogen Leishmania donovani secretes a histidine acid phosphatase activity that is resistant to proteolytic degradation","volume":"51","author":"Joshi","year":"2004","journal-title":"J. Eukaryot. Microbiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1128\/iai.65.2.783-786.1997","article-title":"Proteophosphoglycan secreted by Leishmania mexicana amastigotes causes vacuole formation in macrophages","volume":"65","author":"Peters","year":"1997","journal-title":"Infect. Immun."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2666","DOI":"10.1002\/eji.1830271028","article-title":"Secreted proteophosphoglycan of Leishmania mexicana amastigotes activates complement by triggering the mannan binding lectin pathway","volume":"27","author":"Peters","year":"1997","journal-title":"Eur. J. Immunol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1098\/rspb.1991.0097","article-title":"Chitinase secreted by Leishmania functions in the sandfly vector","volume":"245","author":"Schlein","year":"1991","journal-title":"Proc. Biol. Sci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1111\/j.1462-5822.2008.01132.x","article-title":"Leishmania chitinase facilitates colonization of sand fly vectors and enhances transmission to mice","volume":"10","author":"Rogers","year":"2008","journal-title":"Cell Microbiol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"3847","DOI":"10.1074\/jbc.M412299200","article-title":"Molecular characterization, expression, and in vivo analysis of LmexCht1: The chitinase of the human pathogen, Leishmania mexicana","volume":"280","author":"Joshi","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1017\/S0031182000060522","article-title":"Expression of LPG and GP63 by different developmental stages of Leishmania major in the sandfly Phlebotomus papatasi","volume":"101","author":"Davies","year":"1990","journal-title":"Parasitology"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1590\/S0001-37652006000400006","article-title":"The ubiquitous gp63-like metalloprotease from lower trypanosomatids: In the search for a function","volume":"78","author":"Santos","year":"2006","journal-title":"An. Acad. Bras. Ci\u00eancias"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0166-6851(03)00211-1","article-title":"The major surface protease (MSP or GP63) of Leishmania sp. Biosynthesis, regulation of expression, and function","volume":"132","author":"Yao","year":"2003","journal-title":"Mol. Biochem. Parasitol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/S0166-6851(01)00432-7","article-title":"Targeted gene deletion in Leishmania major identifies leishmanolysin (GP63) as a virulence factor","volume":"120","author":"Joshi","year":"2002","journal-title":"Mol. Biochem. Parasitol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"ra58","DOI":"10.1126\/scisignal.2000213","article-title":"Leishmania GP63 alters host signaling through cleavage-activated protein tyrosine phosphatases","volume":"2","author":"Gomez","year":"2009","journal-title":"Sci. Signal"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Contreras, I., Gomez, M.A., Nguyen, O., Shio, M.T., McMaster, R.W., and Olivier, M. (2010). Leishmania-induced inactivation of the macrophage transcription factor AP-1 is mediated by the parasite metalloprotease GP63. PLoS Pathog., 6.","DOI":"10.1371\/journal.ppat.1001148"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1038\/nrm2617","article-title":"Mechanisms of regulated unconventional protein secretion","volume":"10","author":"Nickel","year":"2009","journal-title":"Nat. Rev. Mol. Cell. Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"R35","DOI":"10.1186\/gb-2008-9-2-r35","article-title":"Proteomic analysis of the secretome of Leishmania donovani","volume":"9","author":"Silverman","year":"2008","journal-title":"Genome Biol."},{"key":"ref_62","first-page":"209","article-title":"The Golgi complex of Trypanosoma cruzi epimastigote forms","volume":"27","author":"Figueiredo","year":"1995","journal-title":"J. Submicrosc. Cytol. Pathol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1016\/j.copbio.2010.06.004","article-title":"Pathways of unconventional protein secretion","volume":"21","author":"Nickel","year":"2010","journal-title":"Curr. Opin. Biotechnol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1242\/jcs.01645","article-title":"Direct transport across the plasma membrane of mammalian cells of Leishmania HASPB as revealed by a CHO export mutant","volume":"118","author":"Stegmayer","year":"2005","journal-title":"J. Cell. Sci."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/0166-6851(94)90077-9","article-title":"Expression of a hydrophilic surface protein in infective stages of Leishmania major","volume":"65","author":"Flinn","year":"1994","journal-title":"Mol. Biochem. Parasitol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1765","DOI":"10.1111\/j.1462-5822.2010.01507.x","article-title":"The stage-regulated HASPB and SHERP proteins are essential for differentiation of the protozoan parasite Leishmania major in its sand fly vector, Phlebotomus papatasi","volume":"12","author":"Sadlova","year":"2010","journal-title":"Cell Microbiol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1111\/j.1600-0854.2009.00921.x","article-title":"Reversible phosphorylation as a molecular switch to regulate plasma membrane targeting of acylated SH4 domain proteins","volume":"10","author":"Tournaviti","year":"2009","journal-title":"Traffic"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"11017","DOI":"10.1074\/jbc.275.15.11017","article-title":"Acylation-dependent protein export in Leishmania","volume":"275","author":"Denny","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"3820","DOI":"10.1242\/jcs.011130","article-title":"SH4-domain-induced plasma membrane dynamization promotes bleb-associated cell motility","volume":"120","author":"Tournaviti","year":"2007","journal-title":"J. Cell. Sci."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1913","DOI":"10.4049\/jimmunol.179.3.1913","article-title":"Nonclassical IL-1 beta secretion stimulated by P2X7 receptors is dependent on inflammasome activation and correlated with exosome release in murine macrophages","volume":"179","author":"Qu","year":"2007","journal-title":"J. Immunol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1959","DOI":"10.1042\/BCJ20200917","article-title":"Understanding amphisomes","volume":"478","author":"Ganesan","year":"2021","journal-title":"Biochem. J."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"jcs246322","DOI":"10.1242\/jcs.246322","article-title":"Microautophagy\u2014Distinct molecular mechanisms handle cargoes of many sizes","volume":"133","author":"Schuck","year":"2020","journal-title":"J. Cell. Sci."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"11384","DOI":"10.1074\/jbc.M512307200","article-title":"Endosome sorting and autophagy are essential for differentiation and virulence of Leishmania major","volume":"281","author":"esteiro","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"294","DOI":"10.4161\/auto.5443","article-title":"Turnover of glycosomes during life-cycle differentiation of Trypanosoma brucei","volume":"4","author":"Herman","year":"2008","journal-title":"Autophagy"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.1016\/j.bbamcr.2006.08.019","article-title":"Metabolic functions of glycosomes in trypanosomatids","volume":"1763","author":"Michels","year":"2006","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_76","first-page":"1541708","article-title":"More than just exosomes: Distinct Leishmania infantum extracellular products potentiate the establishment of infection","volume":"8","author":"Santarem","year":"2019","journal-title":"J. Extracell. Vesicles"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1007\/978-1-0716-0294-2_33","article-title":"Isolation of Extracellular Vesicles from Leishmania spp.","volume":"2116","author":"Vucetic","year":"2020","journal-title":"Methods Mol. Biol."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Gabriel, A.M., Galue-Parra, A., Pereira, W.L.A., Pedersen, K.W., and da Silva, E.O. (2021). Leishmania 360 degrees: Guidelines for Exosomal Research. Microorganisms, 9.","DOI":"10.20944\/preprints202105.0754.v1"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/0014-4894(92)90179-E","article-title":"Leishmania major: Differential regulation of the surface metalloprotease in amastigote and promastigote stages","volume":"75","author":"Schneider","year":"1992","journal-title":"Exp. Parasitol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1905","DOI":"10.1128\/EC.00073-07","article-title":"Internal and surface-localized major surface proteases of Leishmania spp. and their differential release from promastigotes","volume":"6","author":"Yao","year":"2007","journal-title":"Eukaryot Cell"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/S0001-706X(02)00238-3","article-title":"Leishmania model for microbial virulence: The relevance of parasite multiplication and pathoantigenicity","volume":"85","author":"Chang","year":"2003","journal-title":"Acta Trop."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"85154","DOI":"10.1155\/2007\/85154","article-title":"Immune response regulation by leishmania secreted and nonsecreted antigens","volume":"2007","author":"Santarem","year":"2007","journal-title":"J. Biomed. Biotechnol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"104077","DOI":"10.1016\/j.jprot.2020.104077","article-title":"Quantitative analysis of proteins secreted by Leishmania (Viannia) braziliensis strains associated to distinct clinical manifestations of American Tegumentary Leishmaniasis","volume":"232","author":"Berbert","year":"2021","journal-title":"J. Proteom."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1021\/acs.jproteome.1c00244","article-title":"Proteomic Analysis of the Promastigote Secretome of Seven Leishmania Species","volume":"21","author":"Pissarra","year":"2022","journal-title":"J. Proteome Res."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.jprot.2009.08.006","article-title":"Proteomic characterization of the released\/secreted proteins of Leishmania (Viannia) braziliensis promastigotes","volume":"73","author":"Cuervo","year":"2009","journal-title":"J. Proteom."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.molbiopara.2014.07.001","article-title":"Shotgun proteomics to unravel the complexity of the Leishmania infantum exoproteome and the relative abundance of its constituents","volume":"195","author":"Braga","year":"2014","journal-title":"Mol. Biochem. Parasitol."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Douanne, N., Dong, G., Douanne, M., Olivier, M., and Fernandez-Prada, C. (2020). Unravelling the proteomic signature of extracellular vesicles released by drug-resistant Leishmania infantum parasites. PLoS Negl. Trop. Dis., 14.","DOI":"10.1371\/journal.pntd.0008439"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1016\/j.celrep.2015.09.058","article-title":"Exosome Secretion by the Parasitic Protozoan Leishmania within the Sand Fly Midgut","volume":"13","author":"Atayde","year":"2015","journal-title":"Cell Rep."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"103902","DOI":"10.1016\/j.jprot.2020.103902","article-title":"Proteomic analysis of exosomes derived from procyclic and metacyclic-like cultured Leishmania infantum chagasi","volume":"227","author":"Forrest","year":"2020","journal-title":"J. Proteom."},{"key":"ref_90","first-page":"709258","article-title":"Leishmania Exosomes\/Extracellular Vesicles Containing GP63 Are Essential for Enhance Cutaneous Leishmaniasis Development Upon Co-Inoculation of Leishmania amazonensis and Its Exosomes","volume":"11","author":"Fajardo","year":"2021","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Hassani, K., Antoniak, E., Jardim, A., and Olivier, M. (2011). Temperature-induced protein secretion by Leishmania mexicana modulates macrophage signalling and function. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0018724"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"710","DOI":"10.3389\/fimmu.2017.00710","article-title":"Leishmania infantum Exoproducts Inhibit Human Invariant NKT Cell Expansion and Activation","volume":"8","author":"Belo","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"e12140","DOI":"10.1002\/jev2.12140","article-title":"Formation of a protein corona on the surface of extracellular vesicles in blood plasma","volume":"10","author":"Toth","year":"2021","journal-title":"J. Extracell. Vesicles"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1007\/s00018-005-5006-6","article-title":"Mass spectrometry-based proteomics in the life sciences","volume":"62","author":"Lane","year":"2005","journal-title":"Cell Mol. Life Sci."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1017\/S0031182013001388","article-title":"The impact of distinct culture media in Leishmania infantum biology and infectivity","volume":"141","author":"Santarem","year":"2014","journal-title":"Parasitology"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1007\/s11010-015-2366-6","article-title":"A unique, highly conserved secretory invertase is differentially expressed by promastigote developmental forms of all species of the human pathogen, Leishmania","volume":"404","author":"Lyda","year":"2015","journal-title":"Mol. Cell. Biochem."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1111\/j.1550-7408.1994.tb01502.x","article-title":"Secretion of sucrase by Leishmania donovani","volume":"41","author":"Blum","year":"1994","journal-title":"J. Eukaryot. Microbiol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1422674","DOI":"10.1080\/20013078.2017.1422674","article-title":"Efficient ultrafiltration-based protocol to deplete extracellular vesicles from fetal bovine serum","volume":"7","author":"Kornilov","year":"2018","journal-title":"J. Extracell. Vesicles"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1128\/IAI.01419-13","article-title":"Biofilm matrix exoproteins induce a protective immune response against Staphylococcus aureus biofilm infection","volume":"82","author":"Gil","year":"2014","journal-title":"Infect. Immun."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"3835","DOI":"10.1007\/s00436-013-3571-4","article-title":"Immunization with excreted-secreted antigens reduces tissue cyst formation in pigs","volume":"112","author":"Wang","year":"2013","journal-title":"Parasitol. Res."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"639801","DOI":"10.3389\/fcimb.2021.639801","article-title":"Revival of Leishmanization and Leishmanin","volume":"11","author":"Volpedo","year":"2021","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"5654","DOI":"10.1128\/IAI.72.10.5654-5661.2004","article-title":"Immunization with Leishmania major exogenous antigens protects susceptible BALB\/c mice against challenge infection with L. major","volume":"72","author":"Tonui","year":"2004","journal-title":"Infect. Immun."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"579","DOI":"10.4269\/ajtmh.2007.76.579","article-title":"Cross-protection against Leishmania donovani but not L. Braziliensis caused by vaccination with L. Major soluble promastigote exogenous antigens in BALB\/c mice","volume":"76","author":"Tonui","year":"2007","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"4223","DOI":"10.1016\/j.vaccine.2007.02.083","article-title":"Long-lasting protection against canine visceral leishmaniasis using the LiESAp-MDP vaccine in endemic areas of France: Double-blind randomised efficacy field trial","volume":"25","author":"Lemesre","year":"2007","journal-title":"Vaccine"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"2825","DOI":"10.1016\/j.vaccine.2004.11.061","article-title":"Protection against experimental visceral leishmaniasis infection in dogs immunized with purified excreted secreted antigens of Leishmania infantum promastigotes","volume":"23","author":"Lemesre","year":"2005","journal-title":"Vaccine"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"105387","DOI":"10.1016\/j.actatropica.2020.105387","article-title":"Evaluation of canine leishmaniosis vaccine CaniLeish(R) under field conditions in native dog populations from an endemic Mediterranean area-A randomized controlled trial","volume":"205","author":"Velez","year":"2020","journal-title":"Acta Trop."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"6695","DOI":"10.1016\/j.vaccine.2020.08.051","article-title":"Immunoprophylaxis pharmacotherapy against canine leishmaniosis: A systematic review and meta-analysis on the efficacy of vaccines approved in European Union","volume":"38","author":"Calzetta","year":"2020","journal-title":"Vaccine"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1111\/pim.12189","article-title":"Immunostimulatory potential and proteome profiling of Leishmania donovani soluble exogenous antigens","volume":"37","author":"Kumar","year":"2015","journal-title":"Parasite Immunol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"4648","DOI":"10.1128\/IAI.00394-07","article-title":"Leish-111f, a recombinant polyprotein vaccine that protects against visceral Leishmaniasis by elicitation of CD4+ T cells","volume":"75","author":"Coler","year":"2007","journal-title":"Infect. Immun."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"3333","DOI":"10.1016\/j.vaccine.2010.02.089","article-title":"Treatment of canine visceral leishmaniasis by the vaccine Leish-111f+MPL-SE","volume":"28","author":"Trigo","year":"2010","journal-title":"Vaccine"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"6581","DOI":"10.1016\/j.vaccine.2010.07.063","article-title":"A clinical trial to evaluate the safety and immunogenicity of the LEISH-F1+MPL-SE vaccine when used in combination with meglumine antimoniate for the treatment of cutaneous leishmaniasis","volume":"28","author":"Nascimento","year":"2010","journal-title":"Vaccine"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.exppara.2010.06.033","article-title":"Leishmania major: Secreted antigens of Leishmania major promastigotes shift the immune response of the C57BL\/6 mice toward Th2 in vitro","volume":"127","author":"Tabatabaee","year":"2011","journal-title":"Exp. Parasitol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"50190","DOI":"10.1074\/jbc.M209210200","article-title":"Leishmania EF-1alpha activates the Src homology 2 domain containing tyrosine phosphatase SHP-1 leading to macrophage deactivation","volume":"277","author":"Nandan","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"111121","DOI":"10.1016\/j.celrep.2022.111121","article-title":"Leishmania parasites exchange drug-resistance genes through extracellular vesicles","volume":"40","author":"Douanne","year":"2022","journal-title":"Cell Rep."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1007\/s00203-022-02756-6","article-title":"Heavy metal-induced oxidative stress and alteration in secretory proteins in yeast isolates","volume":"204","author":"Bhavya","year":"2022","journal-title":"Arch. Microbiol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1080\/21505594.2017.1325064","article-title":"Signatures of cytoplasmic proteins in the exoproteome distinguish community- and hospital-associated methicillin-resistant Staphylococcus aureus USA300 lineages","volume":"8","author":"Mekonnen","year":"2017","journal-title":"Virulence"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"103464","DOI":"10.1016\/j.jprot.2019.103464","article-title":"Quantitative secretome analysis unravels new secreted proteins in Amphotericin B resistant Leishmania donovani","volume":"207","author":"Garg","year":"2019","journal-title":"J. Proteom."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1535750","DOI":"10.1080\/20013078.2018.1535750","article-title":"Minimal information for studies of extracellular vesicles 2018 (MISEV2018): A position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines","volume":"7","author":"Thery","year":"2018","journal-title":"J. Extracell. Vesicles"}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/10\/12\/2435\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:36:41Z","timestamp":1760146601000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/10\/12\/2435"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,8]]},"references-count":118,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["microorganisms10122435"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms10122435","relation":{},"ISSN":["2076-2607"],"issn-type":[{"type":"electronic","value":"2076-2607"}],"subject":[],"published":{"date-parts":[[2022,12,8]]}}}