Papel do metabolismo de triptofano na filamentação de Candida albicans e seus impactos durante a mucosite induzida por 5-fluorouracil em camundongos

Abstract

Candida albicans is a polymorphic yeast that is a commensal part of the microbiota of the majority of the human population and can be contracted in several anatomical sites, such as the gastrointestinal tract (TGI). In cases of immunometabolics imbalances, such as intestinal mucositis caused by 5-fluorouracil (5-FU), C. albicans can cause an opportunistic infection and if it favors the host nutrients, for example tryptophan (Trp). This study aimed to evaluate the role of tryptophan metabolism by C. albicans in a model of opportunistic infection in mice after chemotherapy. Therefore, some in vitro parameters were evaluated. Thus, the growth, biofilm formation and filamentation of C. albicans were observed in the presence and absence of Trp. As a control amino acid tyrosine was used. Two culture media were used for these tests, Sabouraud broth (SD) as standard culture medium and syntetic low dextrose broth (SLD) as chemically defined culture medium. For in vivo experiments, animals C57BL/6j females of 7-8 weeks were used, these received 1x107 of C. albicans in drinking water for 5 days. Also during this model the animals were treated intraperitoneally with 5-FU (75 mg/kg/day) for 3 days. Thus, clinical parameters, survival, histopathological analysis, fungal and bacterial load in TGI, feces, kidney and liver were evaluated. Euthanasia was performed on the 5th or 8th day of the experimental protocol. Statistical analysis was applied to the two-way analysis of variance (ANOVA) followed by the Tukey or Sidak test. It was considered p≤ 0.05 as statistically significant. It was observed that C. albicans can grow and form biofilm in the presence of Trp and that this amino acid, but not tyrosine, induces the filamentation of this yeast, in a dependent concentration. As for the in vivo data, C. albicans was able to colonize all TGI organs in animals with mucositis, besides having accentuated the clinical picture of the animals, which presented 100% mortality. There was also a bacterial translocation to the liver and cecum in animals with mucositis with and without C. albicans. These results suggest that the in vitro and in vivo systems developed will allow to evaluate the impact of tryptophan metabolism for experimental opportunistic infection by C. albicans after chemotherapy.