AUTHOR=Silva-Rocha Walicyranison P. , de Azevedo Matheus F. , Ferreira Magda R. A. , da Silva Julhiany de Fátima , Svidzinski Terezinha I. E. , Milan Eveline P. , Soares Luiz A. L. , Rocha Keyla B. F. , Uchôa Adriana F. , Mendes-Giannini Maria J. S. , Fusco Almeida Ana M. , Chaves Guilherme M. 

TITLE=Effect of the Ethyl Acetate Fraction of Eugenia uniflora on Proteins Global Expression during Morphogenesis in Candida albicans

JOURNAL=Frontiers in Microbiology

VOLUME=Volume 8 - 2017

YEAR=2017

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2017.01788

DOI=10.3389/fmicb.2017.01788

ISSN=1664-302X

ABSTRACT=Under certain circumstances, Candida albicans may switch from colonizing to infective yeast. Morphogenesis in C. albicans and resistance to oxidative stress is an essential step for establishment of infection. Due to the reduced drug available and  emergence of resistant strains, it is mandatory to search for new therapeutic sources. This study aimed to investigate which proteins are differentially expressed during C. albicans morphogenesis, after cells growth in the presence of the ethyl acetate fraction of Eugenia uniflora. We also evaluated the interaction of the fraction with phagocytosis and performed a murine model of oral candidiasis in the presence of the fraction. Forty-eight isolates of C. albicans from oral cavity were selected and the ethyl acetate fraction of Eugenia uniflora was used at 1000 μg/mL. The isolate 111R, a highly-filamentous strain was used to proteomics, as well as the interaction with proteins associated with morphogenesis. The in vivoresponse to infection was observed in a murine model of oral candidiasis and the toxic action of E. uniflora was observed with the MTT assay. The fraction significantly reduced the phagocytosis of C. albicans (Mean 120.36 ± 36.71 yeasts/100PMNs vs. 44.68 ± 19.84 yeasts/100PMNs). Thirty-nine proteins, related to energy generation, protein and glucose metabolism, cell division, cytoplasmic transport, nucleic acid metabolism, cell structure and stress response were identified with proteomics analysis. Important proteins directly related with cytoskeleton formation were down regulated on treated cells. The infection inthe oral cavity ofthe mice was successfully established andattenuated when C. albicans cells were either pre-incubated in the presence of E. uniflora orwhen the ethyl acetate fraction  was applied to the surface of the oral cavityafter infection. These results were consistent withthe reduction in CFU counting (2.36  vs. 1.85 Log10 CFU/ml) and attenuation of tissue damages observed in the histopathological analysis. The fraction was non-toxic to human cells even at concentrations 8 fold-higher than the oneused in the experiments. E. uniflora may acton essential proteins mainly related to cellular structure, reducing the filamentation and attenuating infection, without causing toxic effect on human cells, suggesting that it may be a future therapeutic alternative for the treatment of Candida infections.