Relationships between Secreted Aspartyl Proteinase 2 and General Control Nonderepressible 4 gene in the Candida albicans resistant to itraconazole under planktonic and biofilm conditions

Braz J Microbiol. 2023 Jun;54(2):619-627. doi: 10.1007/s42770-023-00961-z. Epub 2023 Apr 22.

Abstract

This study aimed to explore the roles of SAP2 and GCN4 in itraconazole (ITR) resistance of C. albicans under different conditions, and their correlations. A total of 20 clinical strains of C. albicans, including 10 ITR resistant strains and 10 sensitive strains, were used. Then, SAP2 sequencing and GCN4 sequencing were performed, and the biofilm formation ability of different C. albicans strains was determined. Finally, real-time quantitative PCR was used to measure the expression of SAP2 and GCN4 in C. albicans under planktonic and biofilm conditions, as well as their correlation was also analyzed. No missense mutations and three synonymous mutation sites, including T276A, G543A, and A675C, were found in SAP2 sequencing. GCN4 sequencing showed one missense mutation site (A106T (T36S)) and six synonymous mutation sites (A147C, C426T, T513C, T576A, G624A and C732T). The biofilm formation ability of drug-resistant C. albicans strains was significantly higher than that of sensitive strains (P < 0.05). Additionally, SAP2 and GCN4 were up-regulated in the ITR-resistant strains, and were both significantly higher in C. albicans under biofilm condition. The mRNA expression levels of SAP2 and GCN4 had significantly positive correlation. The higher expression levels of SAP2 and GCN4 were observed in the ITR-resistant strains of C. albicans under planktonic and biofilm conditions, as well as there was a positive correlation between SAP2 and GCN4 mRNA expression.

Keywords: GCN4; Invasive candidiasis; C. albicans; Itraconazole resistance; SAP2.

MeSH terms

  • Antifungal Agents / pharmacology
  • Aspartic Acid Endopeptidases / genetics
  • Aspartic Acid Proteases* / genetics
  • Candida albicans* / genetics
  • Candida albicans* / metabolism
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism
  • Itraconazole / pharmacology
  • RNA, Messenger / genetics

Substances

  • Itraconazole
  • Fungal Proteins
  • Aspartic Acid Proteases
  • Aspartic Acid Endopeptidases
  • RNA, Messenger
  • Antifungal Agents