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Fungal and host protein persulfidation are functionally correlated and modulate both virulence and antifungal

Monica Sueiro-Olivares1, Jennifer Scott1, Sara Gago1

  • 1Manchester Fungal Infection Group (MFIG), School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom.

Plos Biology
|June 1, 2021
PubMed

Insights

Persulfidation, a key stress response, impacts fungal virulence and host defense against Aspergillus fumigatus. Reduced persulfidation in hosts and fungi increases susceptibility to invasive pulmonary aspergillosis.

Area of Science:

  • Mycology
  • Immunology
  • Biochemistry

Background:

  • Aspergillus fumigatus causes severe lung infections (aspergilloses) in immunocompromised individuals.
  • Host-pathogen interactions depend on rapid adaptation to stress.
  • Persulfidation, a posttranslational modification (PTM), is crucial for stress adaptation.

Purpose of the Study:

  • Investigate the role of persulfidation in fungal virulence.
  • Examine persulfidation's role in antifungal host defense.
  • Identify potential therapeutic targets for invasive pulmonary aspergillosis (IPA).

Main Methods:

  • Studied an Aspergillus fumigatus mutant with altered persulfidation levels.
  • Utilized murine models of infection.
  • Analyzed human genetic data, specifically single nucleotide polymorphisms (SNPs) in the cystathionine γ-lyase (CTH) gene.

Main Results:

  • A. fumigatus mutants with low persulfidation showed increased susceptibility to host killing and reduced virulence.
  • A human SNP in CTH led to reduced cellular persulfidation.
  • Reduced host persulfidation correlated with increased IPA risk in hematopoietic stem cell transplant recipients.
  • Host persulfidation levels directly influenced fungal persulfidation levels.

Conclusions:

  • Persulfidation is vital for both fungal virulence and host antifungal defense.
  • Host persulfidation is a critical factor in preventing invasive pulmonary aspergillosis.
  • Host-pathogen persulfidation levels are functionally correlated, suggesting a novel therapeutic avenue.

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