Genomic Understanding of an Infectious Brain Disease from the Desert

Rhinocladiella mackenziei accounts for the majority of fungal brain infections in the Middle East and is restricted to the arid climate zone between Saudi Arabia and Pakistan. Neurotropic dissemination caused by this fungus has been reported in immunocompromised, but also immunocompetent individuals. If untreated, the infection is fatal. Outside of humans, the environmental niche of R. mackenziei is unknown, and the fungus has been only cultured from brain biopsies. In this paper we describe the whole genome re-sequencing of two Rhinocladiella mackenziei strains from patients in Saudi Arabia and Qatar. We assessed intra-species variation and genetic signatures to uncover the genomic basis of the pathogenesis and potential niche adaptations. We found that the duplicated genes (paralogs) are more susceptible to accumulate significant mutations. Comparative genomics with other filamentous ascomycetes revealed a diverse arsenal of genes likely engaged in pathogenicity, such as the degradation of aromatic compounds and iron acquisition. In addition, intracellular accumulation of trehalose and choline suggest possible adaptations to the conditions of arid climate region. Specifically protein family contractions were found, including short-chain dehydrogenase/reductase SDR, the cytochrome P450 (E-class) and the G-protein beta WD-40 repeat. Gene composition and metabolic potential indicate extremotolerance and hydrocarbon assimilation, suggesting a possible environmental habitat of oil-polluted desert soil.

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