PMID- 31265468 OWN - NLM STAT- MEDLINE DCOM- 20200218 LR - 20200309 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 14 IP - 7 DP - 2019 TI - Proteomic analysis of Paracoccidioides brasiliensis complex isolates: Correlation of the levels of differentially expressed proteins with in vivo virulence. PG - e0218013 LID - 10.1371/journal.pone.0218013 [doi] LID - e0218013 AB - BACKGROUND: Paracoccidioidomycosis (PCM) is a systemic mycosis commonly found in Latin America that is caused by distinct species of Paracoccidioides genus: Paracoccidioides brasiliensis complex (S1, PS2, PS3 and PS4) and Paracoccidioides lutzii. Its pathobiology has been recently explored by different approaches to clarify the mechanisms of host-pathogen interactions underpinning PCM. The diversity of clinical forms of this disease has been attributed to both host- and fungus-related factors. METHODOLOGY/PRINCIPAL FINDINGS: For better understanding of the molecular underpinnings of host-fungus interactions, we evaluated in vivo virulence of nine Paracoccidioides brasiliensis complex isolates and correlated it to protein expression profiles obtained by two-dimensional gel electrophoresis. Based on the recovery of viable fungi from mouse organs, the isolates were classified as those having low, moderate, or high virulence. Highly virulent isolates overexpressed proteins related to adhesion process and stress response, probably indicating important roles of those fungal proteins in regulating the colonization capacity, survival, and ability to escape host immune system reaction. Moreover, highly virulent isolates exhibited enhanced expression of glycolytic pathway enzymes concomitantly with repressed expression of succinyl-CoA ligase beta chain, a protein related to the tricarboxylic acid cycle. CONCLUSIONS/SIGNIFICANCE: Our findings may point to the mechanisms used by highly virulent P. brasiliensis isolates to withstand host immune reactions and to adapt to transient iron availability as strategies to survive and overcome stress conditions inside the host. FAU - do Amaral, Cristiane Candida AU - do Amaral CC AD - Department of Medicine, Discipline of Infectious Diseases, Federal University of Sao Paulo (UNIFESP), Sao Paulo, Brazil. FAU - Fernandes, Geisa Ferreira AU - Fernandes GF AD - Department of Microbiology, Immunology and Parasitology, Discipline of Cellular Biology, Federal University of Sao Paulo (UNIFESP), Sao Paulo, Brazil. FAU - Rodrigues, Anderson Messias AU - Rodrigues AM AD - Department of Microbiology, Immunology and Parasitology, Discipline of Cellular Biology, Federal University of Sao Paulo (UNIFESP), Sao Paulo, Brazil. FAU - Burger, Eva AU - Burger E AD - Department of Microbiology and Immunology, Federal University of Alfenas (UNIFAL), Alfenas, Brazil. FAU - de Camargo, Zoilo Pires AU - de Camargo ZP AUID- ORCID: 0000-0002-2971-7983 AD - Department of Microbiology, Immunology and Parasitology, Discipline of Cellular Biology, Federal University of Sao Paulo (UNIFESP), Sao Paulo, Brazil. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190702 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Fungal Proteins) SB - IM MH - Animals MH - Fungal Proteins/*immunology MH - Gene Expression Regulation, Fungal/*immunology MH - Male MH - Mice MH - Mice, Inbred BALB C MH - *Paracoccidioides/immunology/isolation & purification/pathogenicity MH - Paracoccidioidomycosis/*immunology/pathology PMC - PMC6605636 COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2019/07/03 06:00 MHDA- 2020/02/19 06:00 PMCR- 2019/07/02 CRDT- 2019/07/03 06:00 PHST- 2018/10/18 00:00 [received] PHST- 2019/05/23 00:00 [accepted] PHST- 2019/07/03 06:00 [entrez] PHST- 2019/07/03 06:00 [pubmed] PHST- 2020/02/19 06:00 [medline] PHST- 2019/07/02 00:00 [pmc-release] AID - PONE-D-18-30248 [pii] AID - 10.1371/journal.pone.0218013 [doi] PST - epublish SO - PLoS One. 2019 Jul 2;14(7):e0218013. doi: 10.1371/journal.pone.0218013. eCollection 2019.