PMID- 33322269 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20201230 IS - 2309-608X (Electronic) IS - 2309-608X (Linking) VI - 6 IP - 4 DP - 2020 Dec 11 TI - Immunoproteomic Analysis Reveals Novel Candidate Antigens for the Diagnosis of Paracoccidioidomycosis Due to Paracoccidioides lutzii. LID - 10.3390/jof6040357 [doi] LID - 357 AB - Paracoccidioidomycosis (PCM) is a life-threatening systemic infection caused by the fungal pathogen Paracoccidioides brasiliensis and related species. Whole-genome sequencing and stage-specific proteomic analysis of Paracoccidioides offer the opportunity to profile humoral immune responses against P. lutzii and P. brasiliensis s. str. infection using innovative screening approaches. Here, an immunoproteomic approach was used to identify PCM-associated antigens that elicit immune responses by combining 2-D electrophoresis of P. lutzii and P. brasiliensis proteomes, immunological detection using a gold-standard serum, and mass spectrometry analysis. A total of 16 and 25 highly immunoreactive proteins were identified in P. lutzii and P. brasiliensis, respectively, and 29 were shown to be the novel antigens for Paracoccidioides species, including seven uncharacterized proteins. Among the panel of proteins identified, most are involved in metabolic pathways, carbon metabolism, and biosynthesis of secondary metabolites in both immunoproteomes. Remarkably, six isoforms of the surface-associated enolase in the range of 54 kDa were identified as the major antigens in human PCM due to P. lutzii. These novel immunoproteomes of Paracoccidioides will be employed to develop a sensitive and affordable point-of-care diagnostic assay and an effective vaccine to identify infected hosts and prevent infection and development of human PCM. These findings provide a unique opportunity for the refinement of diagnostic tools of this important neglected systemic mycosis, which is usually associated with poverty. FAU - Rodrigues, Anderson Messias AU - Rodrigues AM AUID- ORCID: 0000-0003-0891-4563 AD - Laboratory of Emerging Fungal Pathogens, Department of Microbiology, Immunology, and Parasitology, Discipline of Cellular Biology, Federal University of Sao Paulo (UNIFESP), Sao Paulo 04023062, Brazil. FAU - Kubitschek-Barreira, Paula Helena AU - Kubitschek-Barreira PH AD - Department of Cellular Biology, Roberto Alcantara Gomes Institute of Biology, Rio de Janeiro State University (UERJ), Rio de Janeiro 20511010, Brazil. FAU - Pinheiro, Breno Goncalves AU - Pinheiro BG AUID- ORCID: 0000-0001-9134-0657 AD - Laboratory of Emerging Fungal Pathogens, Department of Microbiology, Immunology, and Parasitology, Discipline of Cellular Biology, Federal University of Sao Paulo (UNIFESP), Sao Paulo 04023062, Brazil. FAU - Teixeira-Ferreira, Andre AU - Teixeira-Ferreira A AUID- ORCID: 0000-0001-6690-6620 AD - Toxinology Laboratory, Department of Physiology and Pharmacodynamics, Fiocruz, Rio de Janeiro 21040900, Brazil. FAU - Hahn, Rosane Christine AU - Hahn RC AD - Laboratory of Mycology/Research, Faculty of Medicine, Federal University of Mato Grosso, Cuiaba 78060900, Brazil. AD - Julio Muller University Hospital, Federal University of Mato Grosso, Cuiaba 78048902, Brazil. FAU - de Camargo, Zoilo Pires AU - de Camargo ZP AD - Laboratory of Emerging Fungal Pathogens, Department of Microbiology, Immunology, and Parasitology, Discipline of Cellular Biology, Federal University of Sao Paulo (UNIFESP), Sao Paulo 04023062, Brazil. AD - Department of Medicine, Discipline of Infectious Diseases, Federal University of Sao Paulo (UNIFESP), Sao Paulo 04023062, Brazil. LA - eng GR - 2017/27265-5/Fundacao de Amparo a Pesquisa do Estado de Sao Paulo/ GR - 2018/21460-3/Fundacao de Amparo a Pesquisa do Estado de Sao Paulo/ GR - 429594/2018-6/Conselho Nacional de Desenvolvimento Cientifico e Tecnologico/ GR - 88887.177846/2018-00/Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior/ PT - Journal Article DEP - 20201211 PL - Switzerland TA - J Fungi (Basel) JT - Journal of fungi (Basel, Switzerland) JID - 101671827 PMC - PMC7770604 OTO - NOTNLM OT - Paracoccidioides brasiliensis OT - Paracoccidioides lutzii OT - biomarker OT - diagnosis OT - endemic mycosis OT - immunoproteomic OT - paracoccidioidomycosis OT - proteomic OT - serology OT - systemic mycosis COIS- The authors declare no conflict of interest. The funders had no role in the design of the study; the collection, analyses or interpretation of data; the writing of the manuscript; or the decision to publish the results. EDAT- 2020/12/17 06:00 MHDA- 2020/12/17 06:01 PMCR- 2020/12/11 CRDT- 2020/12/16 01:03 PHST- 2020/11/16 00:00 [received] PHST- 2020/12/04 00:00 [revised] PHST- 2020/12/08 00:00 [accepted] PHST- 2020/12/16 01:03 [entrez] PHST- 2020/12/17 06:00 [pubmed] PHST- 2020/12/17 06:01 [medline] PHST- 2020/12/11 00:00 [pmc-release] AID - jof6040357 [pii] AID - jof-06-00357 [pii] AID - 10.3390/jof6040357 [doi] PST - epublish SO - J Fungi (Basel). 2020 Dec 11;6(4):357. doi: 10.3390/jof6040357.