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Mucoricin is a ricin-like toxin that is critical for the pathogenesis of mucormycosis

Sameh S M Soliman1,2, Clara Baldin1,3, Yiyou Gu1

  • 1Division of Infectious Diseases, The Lundquist Institute for Biomedical Innovation, Harbor-University of California at Los Angeles (UCLA) Medical Center, Torrance, CA, USA.

Nature Microbiology
|January 19, 2021
PubMed

Insights

Mucorales fungi produce a lethal toxin, named mucoricin, crucial for virulence in mucormycosis. Antibodies targeting mucoricin show therapeutic potential by neutralizing its damaging effects and preventing lethal outcomes in animal models.

Area of Science:

  • Mycology
  • Infectious Diseases
  • Toxicology

Background:

  • Mucormycosis is a lethal fungal infection caused by Mucorales fungi with poorly understood pathogenesis.
  • Virulence factors of Mucorales fungi are critical for disease development and patient outcomes.

Purpose of the Study:

  • To identify and characterize the key virulence factor produced by Mucorales fungi.
  • To investigate the therapeutic potential of targeting this virulence factor in mucormycosis.

Main Methods:

  • Identification and purification of a fungal toxin from Mucorales.
  • In vitro assays using human cells to assess toxin-induced damage.
  • In vivo studies in mice to evaluate the efficacy of anti-toxin antibodies and RNA interference.
  • Structural and functional analysis of the toxin, comparing it to known toxins like ricin.

Main Results:

  • A 17 kDa toxin, named mucoricin, was identified as a major virulence factor.
  • Mucoricin inhibits protein synthesis via N-glycosylase activity and causes vascular leak.
  • Polyclonal antibodies against mucoricin neutralized its cytotoxic effects and protected mice from mucormycosis.
  • RNA interference targeting mucoricin production attenuated fungal virulence in vitro and in vivo.
  • Mucoricin shares structural and functional similarities with the plant toxin ricin.

Conclusions:

  • Mucoricin is a critical virulence factor in mucormycosis, acting similarly to ricin.
  • Targeting mucoricin with antibodies represents a promising therapeutic strategy for invasive fungal infections.
  • The discovery of mucoricin expands our understanding of toxin production across different kingdoms of life.

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