Novel thiazolinyl-picolinamide-based palladium(II) complex extenuates the virulence and biofilms of vulvovaginal candidiasis (VVC) causing Candida

Int Microbiol. 2024 Oct;27(5):1527-1539. doi: 10.1007/s10123-024-00497-8. Epub 2024 Mar 11.

Abstract

Candida infections are growing all over the world as a result of their resistance to anti-fungal drugs. This raises concerns about public health, particularly in cases of vulvovaginal candidiasis (VVC). Therefore, the need for effective treatment options for Candida infections has become crucial. The main goal of the study is to evaluate the efficacy of novel palladium metal complexes against fluconazole-resistant Candida spp., particularly C. albicans and C. auris. The process begins with identifying the minimum inhibitory concentration (MIC), followed by growth curve assays, colony morphology analysis, characterization, and gene expression analysis. The investigation revealed that sub-MIC of Pd(II) complex B (250 μg/mL) inhibited Candida spp. more effectively than amphotericin B (500 μg/mL). Further, Pd(II) complex B drastically reduced the growth of Candida spp. biofilms by 70-80% for nascent biofilms and 70-75% for mature biofilms. Additionally, the yeast-to-hyphal switch and SEM studies revealed that Pd(II) complex B effectively hinders the growth of drug-resistant Candida cells. The gene expression investigation also evidenced that Pd(II) complex B downregulated virulence genes in C. albicans (ERG, EFG, UME6, and HGC) and C. auris (ERG, CDR, and HGC). The findings showed that Pd(II) complex B effectively inhibited the growth of Candida biofilm formation and was reported as a potential anti-biofilm agent against Candida spp. that are resistant to drugs.

Keywords: Anti-biofilm; Anti-fungal; Biofilm; Metal complexes.

MeSH terms

  • Antifungal Agents* / pharmacology
  • Biofilms* / drug effects
  • Biofilms* / growth & development
  • Candida albicans / drug effects
  • Candida albicans / genetics
  • Candida albicans / pathogenicity
  • Candida albicans / physiology
  • Candida* / drug effects
  • Candida* / genetics
  • Candida* / pathogenicity
  • Candida* / physiology
  • Candidiasis, Vulvovaginal* / drug therapy
  • Candidiasis, Vulvovaginal* / microbiology
  • Coordination Complexes / chemistry
  • Coordination Complexes / pharmacology
  • Drug Resistance, Fungal*
  • Female
  • Fluconazole / pharmacology
  • Humans
  • Microbial Sensitivity Tests*
  • Palladium* / chemistry
  • Palladium* / pharmacology
  • Virulence / drug effects

Substances

  • Antifungal Agents
  • Palladium
  • Fluconazole
  • Coordination Complexes