SummaryCryptococcus neoformans is an opportunistic pathogen responsible for serious disease in humans. Critical for virulence of this fungus is an elaborate polysaccharide capsule, which impedes the host immune response. We found that association of the capsule with the cell requires a specific component of the cell wall, a a a a -1,3-glucan. Post-transcriptional inhibition of a a a a -1,3-glucan synthase expression, using double-stranded RNA interference, yields cells that are unable to assemble a capsule although they generate its polysaccharide components. The resulting cryptococci are slow-growing and acapsular. This finding demonstrates a novel mode of polysaccharide attachment and an important application of RNA interference in fungi. The elimination of the capsule by reducing the expression of a single gene suggests a potential avenue for antifungal chemotherapy.

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SummaryYeast cell walls are critical for maintaining cell integrity, particularly in the face of challenges such as growth in mammalian hosts. The pathogenic fungus Cryptococcus neoformans additionally anchors its polysaccharide capsule to the cell surface via a(1-3) glucan in the wall. Cryptococcal cells disrupted in their alpha glucan synthase gene were sensitive to stresses, including temperature, and showed difficulty dividing. These cells lacked surface capsule, although they continued to shed capsule material into the environment. Electron microscopy showed that the alpha glucan that is usually localized to the outer portion of the cell wall was absent, the outer region of the wall was highly disorganized, and the inner region was hypertrophic. Analysis of cell wall composition demonstrated complete loss of alpha glucan accompanied by a compensatory increase in chitin/chitosan and a redistribution of beta glucan between cell wall fractions. The mutants were unable to grow in a mouse model of infection, but caused death in nematodes. These studies integrate morphological and biochemical investigations of the role of alpha glucan in the cryptococcal cell wall.

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In this Science, Ethics, and Society elective undergraduate course at the St. Louis College of Pharmacy, students consider topics that scientists face continuously, including human and animal subjects, science denial, treatment of scientists, who owns and funds science, personalized medicine and genetics, health disparities, and scientific integrity, all through lenses of inclusion and equity. Students read primary and secondary literature pertaining to each day’s topic, upload reflections to a course management system, and engage in structured dialogue in a facilitated classroom environment. Overarching themes address how women and men and their scientific work have been treated or received differently, as well as particular challenges faced by people of color, members of the LGBTQIA+ community, and those with disabilities. This course helps students see how the culture of science has been created and sustained, how it has not encouraged equal participation, and how it could be shaped differently. Student responses to the course recognize that this approach to the scientific material is valuable and that it does not appear elsewhere in their curriculum.