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Understanding Mucor circinelloides pathogenesis by comparative genomics and phenotypical studies

Loida López-Fernández1, Marta Sanchis1, Patricia Navarro-Rodríguez1

  • 1a Unitat de Microbiologia, Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili and Institut d'Investigació Sanitària Pere Virgili (IISPV) , Reus , Spain.

Virulence
|February 14, 2018
PubMed

Insights

Mucor circinelloides infections are a growing public health threat. Genetic analysis identified a key extracellular protein essential for virulence, offering new targets for combating this fungus.

Area of Science:

  • Mycology
  • Infectious Diseases
  • Genomics

Background:

  • Mucorales infections pose significant public health risks due to high mortality.
  • Mucor circinelloides exhibits strain-dependent virulence, suggesting underlying genetic variations.
  • Understanding the genetic basis of virulence is crucial for developing effective treatments.

Purpose of the Study:

  • To decipher the genetic underpinnings of Mucor circinelloides pathogenicity.
  • To identify specific genes contributing to virulence through comparative genomics.
  • To explore the role of cell wall components and extracellular proteins in fungal pathogenesis.

Main Methods:

  • Whole genome sequencing of an avirulent (NRRL3631) and a virulent (CBS277.49) M. circinelloides strain.
  • Comparative genomic analysis to identify genetic differences, including gene truncations and absences.
  • Phenotypic characterization focusing on heat stress, cell wall composition, and susceptibility to toxic compounds.
  • Gene deletion studies of extracellular protein-coding genes and virulence assessment in murine infection models.

Main Results:

  • Genome comparison revealed 773 genetic differences in the avirulent strain.
  • The virulent strain showed altered cell wall properties and increased tolerance to certain compounds.
  • Deletion of the hypothetical extracellular protein-coding gene ID112092 significantly reduced M. circinelloides virulence.
  • Extracellular and surface proteins play a critical role in M. circinelloides pathogenesis.

Conclusions:

  • Genetic variations, particularly in genes encoding extracellular proteins, are critical for M. circinelloides virulence.
  • The gene ID112092 is a significant contributor to the fungus's pathogenicity.
  • Targeting surface and secreted proteins represents a promising strategy for controlling Mucorales infections.
Keywords:
Fungal pathogenesisGenome comparisonMucorMucormycosisMurine model infectionVirulence factorVirulence factorsWhole genome sequencing

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