Understanding Mucor circinelloides pathogenesis by comparative genomics and phenotypical studies.

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.