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Aspergillus fumigatus FhdA Transcription Factor Is Important for Mitochondrial Activity and Codon Usage Regulation

Ana Cristina Colabardini1, Norman Van Rhijn2, Abigail L LaBella3,4

  • 1Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, São Paulo, Brazil.

Antimicrobial Agents and Chemotherapy
|August 2, 2022
PubMed

Insights

Fungal transcription factor FhdA regulates genes essential for mitochondrial function. This impacts tRNA expression, revealing a novel mechanism of caspofungin tolerance in Aspergillus fumigatus.

Area of Science:

  • Mycology
  • Molecular Biology
  • Antimicrobial Resistance

Background:

  • Aspergillosis is a fungal infection caused by Aspergillus fumigatus.
  • Caspofungin (CSP) is an antifungal drug used to treat aspergillosis.
  • CSP tolerance is a growing clinical concern.
  • The transcription factor FhdA is known to be crucial for mitochondrial activity.

Purpose of the Study:

  • To investigate the role of FhdA in regulating gene expression.
  • To determine FhdA's influence on mitochondrial function during CSP treatment.
  • To elucidate the mechanism underlying CSP tolerance.

Main Methods:

  • Gene expression analysis using RNA sequencing.
  • Assessing the impact of FhdA on RNA polymerase II and III activity.
  • Investigating tRNA expression levels.
  • Evaluating mitochondrial function under CSP stress.

Main Results:

  • FhdA regulates genes transcribed by both RNA polymerase II and III.
  • FhdA influences the expression of specific tRNAs.
  • These tRNAs are critical for maintaining mitochondrial function in the presence of CSP.
  • A novel mechanism of CSP tolerance involving FhdA and tRNA regulation was identified.

Conclusions:

  • FhdA plays a significant role in regulating gene expression beyond mitochondrial activity.
  • FhdA-mediated tRNA regulation is a key factor in Aspergillus fumigatus's response to caspofungin.
  • This discovery opens new avenues for understanding and combating antifungal drug tolerance.
Keywords:
Aspergillus fumigatuscaspofungin paradoxical effectcodon usagegene regulationtranscription factor

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