surface localization of glucosylceramide during cryptococcus neoformans infection allows targeting as a potential antifungal表面的本地化葡糖神经酰胺在新型隐球菌感染允许目标作为一个潜在的抗真菌.pdfVIP

Surface Localization of Glucosylceramide during Cryptococcus neoformans Infection Allows Targeting as a Potential Antifungal 1 1 1 5 5 1 Ryan Rhome , Arpita Singh , Talar Kechichian , Monica Drago , Giulia Morace , Chiara Luberto , Maurizio Del Poeta1,2,3,4* 1 Departments of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, South Carolina, United States of America, 2 Departments of Microbiology and Immunology, Medical University of South Carolina, Charleston, South Carolina, United States of America, 3 Department of Craniofacial Biology, Medical University of South Carolina, Charleston, South Carolina, United States of America, 4 Division of Infectious Diseases, Medical University of South Carolina, Charleston, South Carolina, United States of America, 5 Dipartimento di Sanita’ Pubblica, Microbiologia-Virologia, Universita’ degli Studi di Milano, Milan, Italy Abstract Cryptococcus neoformans (Cn) is a significant human pathogen that, despite current treatments, continues to have a high morbidity rate especially in sub-Saharan Africa. The need for more tolerable and specific therapies has been clearly shown. In the search for novel drug targets, the gene for glucosylceramide synthase (GCS1) was deleted in Cn, resulting in a strain (Dgcs1) that does not produce glucosylceramide (GlcCer) and is avirulent in mouse models of infection. To understand the biology behind the connection between virulence and GlcCer, the production and localization of GlcCer must be characterized in conditions that are prohibitive to the growth of Dgcs1 (neutral pH and high CO2). These prohibitive conditions are physiologically similar to those found in the ex