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Secreted aspartyl protease 3 regulated by the Ras/cAMP/PKA pathway promotes the virulence of Candida auris

  • Ji Seok Kim
  • , Kyung Tae Lee
  • , Yong Sun Bahn*
  • *Corresponding author for this work
  • Yonsei University

Research output: Contribution to journalJournal articlepeer-review

Abstract

The surge of multidrug-resistant fungal pathogens, especially Candida auris, poses significant threats to global public health. Candida auris exhibits resistance to multiple antifungal drugs, leading to major outbreaks and a high mortality rate. With an urgent call for innovative therapeutic strategies, this study focused on the regulation and pathobiological significance of secreted aspartyl proteinases (SAPs) in C. auris, as these enzymes play pivotal roles in the virulence of some fungal species. We delved into the Ras/cAMP/PKA signaling pathway’s influence on SAP activity in C. auris. Our findings underscored that the Ras/cAMP/PKA pathway significantly modulates SAP activity, with PKA catalytic subunits, Tpk1 and Tpk2, playing a key role. We identified a divergence in the SAPs of C. auris compared to Candida albicans, emphasizing the variation between Candida species. Among seven identified secreted aspartyl proteases in C. auris (Sapa1 to Sapa7), Sapa3 emerged as the primary SAP in the pathogen. Deletion of Sapa3 led to a significant decline in SAP activity. Furthermore, we have established the involvement of Sapa3 in the biofilm formation of C. auris. Notably, Sapa3 was primarily regulated by Tpk1 and Tpk2. Deletion of SAPA3 significantly reduced C. auris virulence, underscoring its pivotal role in C. auris pathogenicity. The outcomes of this study provide valuable insights into potential therapeutic targets, laying the groundwork for future interventions against C. auris infection.

Original languageEnglish
Article number1257897
JournalFrontiers in Cellular and Infection Microbiology
Volume13
DOIs
StatePublished - 2023

Keywords

  • a human fungal pathogen
  • C. auris
  • Ras/cAMP/PKA signaling pathway
  • Sapa3
  • secreted aspartyl proteinase
  • virulence

Quacquarelli Symonds(QS) Subject Topics

  • Medicine
  • Biological Sciences

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