Methamphetamine Enhances Cryptococcus neoformans Melanization, Antifungal Resistance, and Pathogenesis in a Murine Model of Drug Administration and Systemic Infection.

Methamphetamine (METH) is a major public health and safety problem in the United States. Chronic METH abuse is associated with a 2-fold-higher risk of HIV infection and, possibly, additional infections, particularly those that enter through the respiratory tract or skin. Cryptococcus neoformans is an encapsulated opportunistic yeast-like fungus that is a relatively frequent cause of meningoencephalitis in immunocompromised patients, especially in individuals with AIDS. C. neoformans melanizes during mammalian infection in a process that presumably uses host-supplied compounds such as catecholamines. l-3,4-Dihydroxyphenylalanine (l-Dopa) is a natural catecholamine that is frequently used to induce melanization in C. neoformans. l-Dopa-melanized cryptococci manifest resistance to radiation, phagocytosis, detergents, and heavy metals. Using a systemic mouse model of infection and in vitro assays to critically assess the impact of METH on C. neoformans melanization and pathogenesis, we demonstrated that METH-treated mice infected with melanized yeast cells showed increased fungal burdens in the blood and brain, exacerbating mortality. Interestingly, analyses of cultures of METH-exposed cryptococci supplemented with l-Dopa revealed that METH accelerates fungal melanization, an event of adaptation to external stimuli that can be advantageous to the fungus during pathogenesis. Our findings provide novel evidence of the impact of METH abuse on host homeostasis and increased permissiveness to opportunistic microorganisms.

Reduced phagocytosis and killing of Cryptococcus neoformans biofilm-derived cells by J774.16 macrophages is associated with fungal capsular production and surface modification.

Cryptococcus neoformans is an opportunistic encapsulated pathogen that causes life-threatening meningoencephalitis in individuals with immunosuppression. We compared the interactions of C. neoformans planktonic and biofilm-derived cells with J774.16 macrophage-like cells. Planktonic cells are more phagocytized and killed by J774.16 cells than biofilm-derived fungal cells. Biofilm-derived cryptococci possess larger capsule size and release significantly more capsular polysaccharide than planktonic cells in culture. Biofilm-derived fungi exhibited upregulation of genes involved in capsular production. Capsular-specific monoclonal antibody 18B7 demonstrated differential binding to the surface of planktonic and biofilm-derived cryptococci providing a plausible strategy for fungal evasion of macrophages and persistence. Future studies are necessary to elucidate how C. neoformans biofilm-derived cells regulate their virulence factors when interacting with cells of the immune system.

Coccidioidomycosis: Epidemiology, Fungal Pathogenesis, and Therapeutic Development.

PURPOSE OF REVIEW: Coccidioidomycosis can result from the inhalation of infectious spores of Coccidioides species (spp.) immitis or posadasii. Clinical manifestations range from mild flu-like disease to severe disseminated infection that can require life-long therapy. Burden of this mycosis is high in the southwest region of the USA where it is well characterized, and in many areas of Mexico and Latin America where it is inadequately characterized. Here, we provide historical data and current knowledge on Coccidioides spp. pathogenesis as well as recent progress in therapeutic and vaccine development against coccidioidomycosis. RECENT FINDINGS: The virulence mechanisms of Coccidioides spp. are largely unknown; however, production and regulation of a spherule glycoprotein, ammonium production, and melanization have all been proposed as integral factors in Coccidioides spp.' pathogenesis. Therapeutic options are limited and not 100% effective, but individualized treatment with triazoles or amphotericin B over the course of pulmonary or disseminated infection can be effective in resolution of coccidioidomycosis. Human immunization has not been achieved but efforts are ongoing. SUMMARY: Advances in therapeutic and vaccine development are imperative for the prevention and treatment of coccidioidomycosis, especially for those individuals at risk either living or traveling to or from endemic areas.

Relationship of environmental disturbances and the infectious potential of fungi.

Fungi are critical organisms for the environment and offer many benefits to modern society through their application in the pharmaceutical, beverage and food industries. In contrast, fungal pathogens are emerging threats to humans, animals, plants and insects with potential to cause devastating mortality, morbidity and economic loss. Outbreaks associated with anthropogenic alterations of the environment, including climate change-related events such as natural disasters, are responsible for human, animal and plant disease. Similarly, fungi and their metabolites also have a negative impact in agriculture, posing a serious threat to our food supplies. Here, we describe the existing knowledge and importance of understanding the relationship of fungi and the environment in the context of human, animal and plant disease. Our goal is to encourage communication between scientists and the general public to create informed awareness about the impact of fungi in their daily lives and their environment.