Convergent and divergent roles of the glucose-responsive kinase SNF4 in Candida tropicalis

Virulence. 2023 Dec;14(1):2175914. doi: 10.1080/21505594.2023.2175914.

Abstract

The sucrose non-fermenting 1 (SNF1) complex is a heterotrimeric protein kinase complex that is an ortholog of the mammalian AMPK complex and is evolutionally conserved in most eukaryotes. This complex contains a catalytic subunit (Snf1), a regulatory subunit (Snf4) and a scaffolding subunit (Sip1/Sip2/Gal73) in budding yeast. Although the function of AMPK has been well studied in Saccharomyces cerevisiae and Candida albicans, the role of AMPK in Candida tropicalis has never been investigated. In this study, we focused on SNF4 in C. tropicalis as this fungus cannot produce a snf1Δ mutant. We demonstrated that C. tropicalis SNF4 shares similar roles in glucose derepression and is necessary for cell wall integrity and virulence. The expression of both SNF1 and SNF4 was significantly induced when glucose was limited. Furthermore, snf4Δ strains exhibited high sensitivity to many surface-perturbing agents because the strains contained lower levels of glucan, chitin and mannan. Interestingly, in contrast to C. albicans sak1Δ and snf4Δ, C. tropicalis snf4Δ exhibited phenotypes for cell aggregation and pseudohypha production. These data indicate that SNF4 performs convergent and divergent roles in C. tropicalis and possibly other unknown roles in the C. tropicalis SNF1-SNF4 AMPK pathway.

Keywords: AMPK; Candida tropicalis; SNF4; cell wall integrity; glucose derepression; virulence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases* / genetics
  • AMP-Activated Protein Kinases* / metabolism
  • Animals
  • Candida tropicalis* / genetics
  • Glucose / metabolism
  • Mammals
  • Protein Serine-Threonine Kinases* / genetics
  • Protein Serine-Threonine Kinases* / metabolism
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae Proteins / genetics
  • Transcription Factors / genetics

Substances

  • AMP-Activated Protein Kinases
  • Glucose
  • Protein Serine-Threonine Kinases
  • Saccharomyces cerevisiae Proteins
  • SNF4 protein, S cerevisiae
  • Transcription Factors

Grants and funding

The work was supported by the National Science and Technology Council [111-2320-B-002 -070].