Unlabelled: The ability to sense, import but also detoxify copper (Cu) has been shown to be crucial for microbial pathogens to survive within the host. Previous studies conducted with the opportunistic human fungal pathogen ( ) have revealed two extreme Cu environments encountered during infection: A high Cu environment within the lung and a low Cu environment within the brain. However, how senses these different host Cu microenvironments, and the consequences of a blunted Cu stress adaption for pathogenesis, are not well understood.
View Article and Find Full Text PDFCryptococcal meningitis (CM) causes significant global morbidity and mortality. Current therapeutic strategies rely on deoxycholated or liposomal forms of the polyene amphotericin B. Nystatin is also a polyene with broad-spectrum antimicrobial activity.
View Article and Find Full Text PDFTrehalose-6-phosphate synthase (TPS1) was identified as a virulence factor for and a promising therapeutic target. This study reveals previously unknown roles of TPS1 in evasion of host defenses during pulmonary and disseminated phases of infection. In the pulmonary infection model, TPS1-deleted () are rapidly cleared by mouse lungs whereas TPS1-sufficent WT (H99) and revertant (:) strains expand in the lungs and disseminate, causing 100% mortality.
View Article and Find Full Text PDFCryptococcal meningitis (CM) is a fungal disease caused by the invasion of Cryptococcus yeast cells into the central nervous system. The organism is thought to enter the body through the lungs and then escape due to dysregulation of the immune response. Multiple animal species have been used to model the infection and characterize CM including mice, rats, dogs, guinea pigs, and rabbits.
View Article and Find Full Text PDFInvasive fungal infections are a significant public health concern, with mortality rates ranging from 20% to 85% despite current treatments. Therefore, we examined whether a ketogenic diet could serve as a successful treatment intervention in murine models of and infection in combination with fluconazole-a low-cost, readily available antifungal therapy. The ketogenic diet is a high-fat, low-carbohydrate diet that promotes fatty acid oxidation as an alternative to glycolysis through the production of ketone bodies.
View Article and Find Full Text PDF