Genomic Understanding of an Infectious Brain Disease from the Desert

Area of Science:

• Mycology
• Genomics
• Pathogenomics

Background:

• Rhinocladiella mackenziei is a significant cause of fungal brain infections in the Middle East, prevalent in arid regions.
• This fungus can cause neurotropic dissemination in both immunocompromised and immunocompetent individuals, leading to fatal outcomes if untreated.
• The environmental niche and non-human reservoirs of R. mackenziei remain largely unknown, with isolation primarily from human brain biopsies.

Purpose of the Study:

• To perform whole-genome resequencing of R. mackenziei strains from Saudi Arabia and Qatar.
• To investigate intraspecies variation and genetic signatures to understand the genomic basis of pathogenesis.
• To identify potential genomic adaptations related to the fungus's survival in arid climates and its pathogenic potential.

Main Methods:

• Whole-genome resequencing of two R. mackenziei strains.
• Comparative genomics analysis with other filamentous ascomycetes.
• Assessment of intraspecies variation, gene duplication impacts, and protein family contractions.

Main Results:

• Duplicated genes (paralogs) showed higher susceptibility to mutations.
• Identification of a gene arsenal for pathogenicity, including aromatic compound degradation and iron acquisition pathways.
• Evidence of adaptations to arid conditions, such as intracellular trehalose and choline accumulation, and protein family contractions (SDR, CYP, WD-40 repeat).

Conclusions:

• Genomic analysis provides insights into the pathogenic mechanisms and niche adaptations of R. mackenziei.
• The fungus exhibits extremotolerance and hydrocarbon assimilation capabilities.
• Oil-polluted desert soil is proposed as a potential environmental habitat for R. mackenziei.