FUNGICIDE-DRIVEN DRUG RESISTANCE IN CANDIDA TROPICALIS

FUNGICIDE-DRIVEN DRUG RESISTANCE IN CANDIDA TROPICALIS

Why in the News?

  • Candida tropicalis, a deadly fungal pathogen in India, shows growing resistance to antifungal drugs like fluconazole and voriconazole.
  • A study in PLoS Biology links this resistance to tebuconazole, a widely used agricultural fungicide.
  • The resistant strains display aneuploidy (abnormal chromosome numbers), enabling stronger drug tolerance.

FUNGICIDE-DRIVEN DRUG RESISTANCE IN CANDIDA TROPICALIS

How Resistance Develops in Fungal Strains

  • Drug exposure: Researchers exposed C. tropicalis strains to increasing doses of tebuconazole, generating 35 resistant colonies.
  • Cross-resistance: These strains became resistant not only to tebuconazole but also to fluconazole and voriconazole.
  • Genomic changes: Resistance emerged via segmental aneuploidy, such as duplications of genes like TAC1 (ABC-transporter regulator) and deletion of HMG1, which altered ergosterol synthesis.
  • Trade-off observed: Strains showed slower growth without drugs but higher survival in antifungal environments.

Unexpected Discovery: Stable Haploid Strains

  • Haploid finding: Researchers found stable haploid strains among the resistant colonies—rare in fungi.
  • Mating potential: Haploids could mate, suggesting possible gene spread of resistance in the wild.
  • Global confirmation: Two natural haploids were also identified among 868 clinical strains, including some from Spain.

ANTIMICROBIAL RESISTANCE (AMR)

●Definition: AMR is when microbes evolve to resist antimicrobial agents, making treatments ineffective.

●Fungal AMR concern: Overuse of azole fungicides in agriculture leads to clinical cross-resistance.

●Impact: Resistant fungal strains can cause severe infections with high mortality, limiting drug options.

●Global response: WHO highlights AMR as a top global threat, calling for regulation of drug use across sectors.