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 resequencing of two R. mackenziei strains from patients in Saudi Arabia and Qatar. We assessed intraspecies 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 accumulating 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 suggests possible adaptations to the conditions of an arid climate region. Specifically, protein family contractions were found, including short-chain dehydrogenase/reductase SDR, the cytochrome P450 (CYP) (E-class), and the G-protein ß WD-40 repeat. Gene composition and metabolic potential indicate extremotolerance and hydrocarbon assimilation, suggesting a possible environmental habitat of oil-polluted desert soil.

Management of mycetoma: major challenge in tropical mycoses with limited international recognition.

PURPOSE OF REVIEW: The present review highlights an orphan infectious disease in alarming need of international recognition. While money is being invested to develop new broad-spectrum antimicrobial drugs to treat infection in general, improvement in the management of complicated infections such as mycetoma receives little support. RECENT FINDINGS: Many case presentations describe single-center experience in the management of mycetoma. Unfortunately, randomized and blinded clinical studies into the efficacy of antimicrobial treatment are desperately lacking. Response to medical treatment is usually better in actinomycetoma than eumycetoma. Eumycetoma is difficult to treat using current therapies. Surgery in combination with azole treatment is the recommended regimen for small eumycetoma lesions in the extremities. Bone involvement complicates clinical management, leaving surgical amputation as the only treatment option. Although clinical management has not received major attention recently, laboratory technology has improved in areas of molecular diagnosis and epidemiology. SUMMARY: Management of mycetoma and laboratory diagnosis of its etiological agents need to be improved and better implemented in endemic regions. Optimized therapeutic approaches and more detailed epidemiological data are urgently needed. It is vital to initiate multicenter collaborations on national and international levels to develop consensus clinical score sheets and state-of-the-art treatment regimens for mycetoma patients.