PMID- 32998395 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20201222 IS - 2309-608X (Electronic) IS - 2309-608X (Linking) VI - 6 IP - 4 DP - 2020 Sep 28 TI - Paracoccidioides HSP90 Can Be Found in the Cell Surface and Is a Target for Antibodies with Therapeutic Potential. LID - 10.3390/jof6040193 [doi] LID - 193 AB - Paracoccidioidomycosis (PCM) is one of the most frequent systemic mycoses in Latin America. It affects mainly male rural workers in impoverished regions, and the therapy can last up to two years or use drugs that are very toxic. Given the need for novel safe and effective approaches to treat PCM, we have been developing monoclonal antibodies (mAbs) that could be used not only to block specific fungal targets, but also modulate the host's antifungal immunity. In this work we show the generation of and promising results with an mAb against Heat Shock Protein (HSP)90, a molecular chaperone that is an important virulence factor in fungi. Using recombinant Paracoccidioides lutzii (Pb01) and P. brasiliensis (Pb18) HSP90 proteins produced in E. coli, we immunized mice and generated polyclonal antibodies and an IgG1 hybridoma mAb. The proteins were very immunogenic and both the polyclonal serum and mAb were used in immunofluorescence experiments, which showed binding of antibodies to the yeast cell surface. The mAb successfully opsonized P. lutzii and P. brasiliensis cells in co-incubations with J774.16 macrophage-like cells. Our results suggest that this mAb could serve as the basis for new immunotherapy regimens for PCM. FAU - Moura, Agata Nogueira D'Aurea AU - Moura AND AUID- ORCID: 0000-0003-0480-5028 AD - Institute of Tropical Medicine, Department of Dermatology, Faculty of Medicine, University of Sao Paulo, Sao Paulo 05403-000, SP, Brazil. FAU - Oliveira, Diane Sthefany Lima de AU - Oliveira DSL AUID- ORCID: 0000-0002-2655-4672 AD - Institute of Biological Sciences, University of Brasilia, Brasilia 70910-900, DF, Brazil. FAU - Paredes, Verenice AU - Paredes V AD - Karan Technologies Research and Development, Brasilia 70632-200, DF, Brazil. AD - Faculty of Medicine, University of Brasilia, Brasilia 70910-900, DF, Brazil. FAU - Rocha, Leticia Barboza AU - Rocha LB AUID- ORCID: 0000-0001-7832-058X AD - Bacteriology Laboratory, Butantan Institute, Sao Paulo 05503-900, SP, Brazil. FAU - Oliveira, Fabiana Freire Mende de AU - Oliveira FFM AD - Faculty of Medicine, University of Brasilia, Brasilia 70910-900, DF, Brazil. FAU - Lessa, Gustavo Meirelles AU - Lessa GM AD - Faculty of Medicine, University of Brasilia, Brasilia 70910-900, DF, Brazil. FAU - Riasco-Palacios, Juan Fernando AU - Riasco-Palacios JF AUID- ORCID: 0000-0002-9170-1034 AD - Faculty of Medicine, University of Brasilia, Brasilia 70910-900, DF, Brazil. FAU - Casadevall, Arturo AU - Casadevall A AUID- ORCID: 0000-0002-9402-9167 AD - Department of Molecular Microbiology & Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA. FAU - Albuquerque, Patricia AU - Albuquerque P AUID- ORCID: 0000-0001-8160-7784 AD - Faculty of Ceilandia, University of Brasilia, Brasilia 72220-275, DF, Brazil. FAU - Felipe, Maria Sueli Soares AU - Felipe MSS AD - Institute of Biological Sciences, University of Brasilia, Brasilia 70910-900, DF, Brazil. AD - Graduate Program in Genomic Sciences and Biotechnology, Catholic University of Brasilia, Brasilia 70790-160, DF, Brazil. FAU - Piazza, Roxane Maria Fontes AU - Piazza RMF AD - Bacteriology Laboratory, Butantan Institute, Sao Paulo 05503-900, SP, Brazil. FAU - Nicola, Andre Moraes AU - Nicola AM AUID- ORCID: 0000-0001-8656-5835 AD - Karan Technologies Research and Development, Brasilia 70632-200, DF, Brazil. AD - Faculty of Medicine, University of Brasilia, Brasilia 70910-900, DF, Brazil. AD - Graduate Program in Genomic Sciences and Biotechnology, Catholic University of Brasilia, Brasilia 70790-160, DF, Brazil. LA - eng GR - R01 HL059842/HL/NHLBI NIH HHS/United States GR - 0193.001048/2015/Fundacao de Apoio a Pesquisa do Distrito Federal/ GR - 193.001.533/2016/Fundacao de Apoio a Pesquisa do Distrito Federal/ GR - 437484/2018-1/Conselho Nacional de Desenvolvimento Cientifico e Tecnologico/ GR - 2015/17178-2/Fundacao de Amparo a Pesquisa do Estado de Sao Paulo/ PT - Journal Article DEP - 20200928 PL - Switzerland TA - J Fungi (Basel) JT - Journal of fungi (Basel, Switzerland) JID - 101671827 PMC - PMC7712200 OTO - NOTNLM OT - HSP90 OT - Paracoccidioides spp. OT - monoclonal antibody COIS- The authors declare that they have no conflict of interest. EDAT- 2020/10/02 06:00 MHDA- 2020/10/02 06:01 PMCR- 2020/09/28 CRDT- 2020/10/01 01:01 PHST- 2020/08/09 00:00 [received] PHST- 2020/09/05 00:00 [revised] PHST- 2020/09/10 00:00 [accepted] PHST- 2020/10/01 01:01 [entrez] PHST- 2020/10/02 06:00 [pubmed] PHST- 2020/10/02 06:01 [medline] PHST- 2020/09/28 00:00 [pmc-release] AID - jof6040193 [pii] AID - jof-06-00193 [pii] AID - 10.3390/jof6040193 [doi] PST - epublish SO - J Fungi (Basel). 2020 Sep 28;6(4):193. doi: 10.3390/jof6040193.