Aspergillus fumigatus cytochrome c impacts conidial survival during sterilizing immunity

mSphere. 2023 Dec 20;8(6):e0030523. doi: 10.1128/msphere.00305-23. Epub 2023 Oct 12.

Abstract

Aspergillus fumigatus can cause a life-threatening infection known as invasive pulmonary aspergillosis (IPA), which is marked by fungus-attributable mortality rates of 20%-30%. Individuals at risk for IPA harbor genetic mutations or incur pharmacologic defects that impair myeloid cell numbers and/or function, exemplified by bone marrow transplant recipients, patients that receive corticosteroid therapy, or patients with chronic granulomatous disease (CGD). However, treatments for Aspergillus infections remain limited, and resistance to the few existing drug classes is emerging. Recently, the World Health Organization classified A. fumigatus as a critical priority fungal pathogen. Our cell death research identifies an important aspect of fungal biology that impacts susceptibility to leukocyte killing. Furthering our understanding of mechanisms that mediate the outcome of fungal-leukocyte interactions will increase our understanding of both the underlying fungal biology governing cell death and innate immune evasion strategies utilized during mammalian infection pathogenesis. Consequently, our studies are a critical step toward leveraging these mechanisms for novel therapeutic advances.

Keywords: Aspergillus fumigatus; cytochrome c; fungal virulence; reactive oxygen species; sterilizing immunity.

MeSH terms

  • Animals
  • Aspergillus fumigatus* / metabolism
  • Cytochromes c / metabolism
  • Humans
  • Invasive Pulmonary Aspergillosis* / microbiology
  • Invasive Pulmonary Aspergillosis* / pathology
  • Mammals
  • Spores, Fungal
  • Sterilizing Immunity
  • Virulence

Substances

  • Cytochromes c