Galgiani, J. N. (2013). Elements of style in managing coccidioidomycosis. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 56(11), 1586-8.
BRASS, C., GALGIANI, J. N., BLASCHKE, T. F., DEFELICE, R., OREILLY, R. A., & STEVENS, D. A. (1982). DISPOSITION OF KETOCONAZOLE, AN ORAL ANTIFUNGAL, IN HUMANS. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 21(1), 151-158.
Sampaio, E. P., Hsu, A. P., Pechacek, J., Bax, H. I., Dias, D. L., Paulson, M. L., Chandrasekaran, P., Rosen, L. B., Carvalho, D. S., Ding, L., Vinh, D. C., Browne, S. K., Datta, S., Milner, J. D., Kuhns, D. B., Long Priel, D. A., Sadat, M. A., Shiloh, M., De Marco, B., , Alvares, M., et al. (2013). Signal transducer and activator of transcription 1 (STAT1) gain-of-function mutations and disseminated coccidioidomycosis and histoplasmosis. The Journal of allergy and clinical immunology, 131(6), 1624-34.
Impaired signaling in the IFN-γ/IL-12 pathway causes susceptibility to severe disseminated infections with mycobacteria and dimorphic yeasts. Dominant gain-of-function mutations in signal transducer and activator of transcription 1 (STAT1) have been associated with chronic mucocutaneous candidiasis.
Shubitz, L. F., Trinh, H. T., Perrill, R. H., Thompson, C. M., Hanan, N. J., Galgiani, J. N., & Nix, D. E. (2014). Modeling nikkomycin Z dosing and pharmacology in murine pulmonary coccidioidomycosis preparatory to phase 2 clinical trials. The Journal of infectious diseases, 209(12), 1949-54.
Nikkomycin Z (NikZ) is a chitin synthase inhibitor with activity against Coccidioides species that is being developed as a first-in-class orphan product for treatment of coccidioidomycosis. It has previously been shown to reduce lethal respiratory infections in mice to undetectable levels when treatment is begun 48 hours after infection. The studies described here focus on bracketing NikZ doses for phase 2 and 3 clinical trials, using an established mouse respiratory infection as a model and starting treatment 120 hours after infection. A dose of 80 mg/kg/day, divided into 2 doses, nearly eradicated infection, and larger doses did not improve fungal clearance. Increasing the duration of treatment from 1 week to 3 weeks resulted in a greater percentage of culture-negative mice. Comparative data show that plasma levels of NikZ that nearly eradicate Coccidioides in mice are achievable in patients and provide a plausibly effective dose range for initial phase 2 clinical studies.
Li, L., Schmelz, M., Kellner, E. M., Galgiani, J. N., & Orbach, M. J. (2007). Nuclear labeling of Coccidioides posadasii with green fluorescent protein. Annals of the New York Academy of Sciences, 1111, 198-207.
Coccidioidomycosis is a mild to life-threatening disease in otherwise healthy humans and other mammals caused by the fungus Coccidioides spp. Understanding the development of the unique dimorphic life cycle of Coccidioides spp. and its role in pathogenesis has been an area of research focus. However, nuclear behavior during the saprobic and parasitic life cycle has not been studied intensively. In this study, green fluorescent protein (GFP) was fused to histone H1 and introduced into Coccidioides posadasii (C. posadasii) strain Silveira to monitor the nuclear behavior of the fungus during the saprobic and parasitic stages of the life cycle. We constructed an Agrobacterium tumefaciens-mediated transformation (ATMT) vector that had in its T-DNA region a hygromycin-resistance gene as well as the fused histone H1-GFP gene under the control of the histone H3 promoter of C. posadasii. More than 30 hygromycin-resistant transformants were obtained and 23 were purified to homozygosity through multiple passages of the original transformants on hygromycin-containing media. One strain (VFC1420) transformed with a single copy of the fusion histone H1-GFP gene was selected for cytological studies. Strong nuclear-localized GFP signals were observed in arthroconidia, hyphae, as well as in spherules and endospores developed in vitro. Thus GFP can be used to study the expression pattern of potential virulence genes identified in serial analysis of gene expression (SAGE) or expressed sequence tags (EST) libraries, and could be a useful tool to monitor disease development in the murine model.
