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has been cited by the following article:

• TITLE: Bacteroides fragilis Supernatant Extracts Enriched in Phenylacetic Acid Induce a Cytotoxic Effect in Mammalian Cells

  AUTHORS: Laís S. Falcão, Eduardo N. F. Antunes, Eliane O. Ferreira, Heidi Pauer, Maria Teresa V. Romanos, Rossiane C. Vommaro, Sérgio H. Seabra, Daniela S. Alviano, Celuta S. Alviano, Antonio Jorge R. da Silva, Leandro A. Lobo, Regina Maria C. P. Domingues

  KEYWORDS: Bacteroides fragilis, Vacuolization, Apoptosis, Vero cells Lineage, Peritoneal Macrophages, Phenylacetic Acid

  JOURNAL NAME: Advances in Microbiology, Vol.5 No.10, September 30, 2015

  ABSTRACT: Bacteroides species are nearly half of the fecal flora community and some are host symbionts crucial to host nutrition and systemic immunity. Among Bacteroides species B. fragilis strains are considered to be the opportunistic ones, being the most isolated anaerobic bacteria in clinical samples. Cell-free supernatants of 65 B. fragilis strains were assayed and they were capable of inducing vacuolating phenotype on Vero cells lineage. The supernatant of the Bacteroides fragilis ATCC 23745 strain was elicited to have the strongest vacuolating effect on Vero cells monolayers and peritoneal macrophages. Some drastic cell alterations were observed, such as a general disorganization of cytoplasm and chromatin condensation, evidencing cell death. By transmission electron microscopy it was confirmed that the vacuoles observed were, in fact, swollen mitochondria. An immunocytochemical assay, TUNEL, was used to confirm this hypothesis and showed that Vero cells and peritoneal macrophages were dying by apoptotic process after exposition of B. fragilis cell-free supernatant. Physical analysis of the apoptotic factor has revealed properties similar to short-chain fatty acids. After gas chromatography and mass spectrometry analysis, phenylacetic acid (PA) was characterized as the major compound present in the most purified active fraction. We believe that the PA is responsible for the pro-apoptotic effect elicited by the supernatant of B. fragilis cultures.