Filogenia e bioprospecção de mutações no gene ERG11 de isolados clínicos do gênero Candida

Abstract

Candida species have great clinical relevance because of the incidence of colonization and infection in humans. In some cases these have shown resistance to antifungal agents, mainly to azoles. The main target of azoles is the key enzyme (lanosterol 14α- demethylase or Erg11p) in the ergosterol biosynthetic pathway, encoded by ERG11 gene. Thus changes in this gene may lead to decreased affinity of azoles for their target and thus lead to drug resistance. The aim was to identify mutations in the coding region of ERG11 gene in clinical isolates of Candida, with the azole resistance profile. Therefore, we amplified the coding regions of ERG11 gene from clinical isolates of Candida with resistance profile established for fluconazole, itraconazole and voriconazole. In addition to the identification of mutations was also established the phylogenetic relationship and built haplotype network between Candida species, it was possible to see differences between the sequences, contributing to the understanding of evolutionary history. This study promoted the identification of new mutations in the coding region of ERG11 gene in clinical isolates of Candida, especially the mutation of meaning changed, A497C (Y166S), which can be associated with resistance to voriconazole in C. krusei. This genetic change, if proven its association, can generate information for the exploration of new therapeutic targets and development of new drugs for Candida species resistant to azoles.