Glycans of the Pathogenic Yeast Cryptococcus neoformans and Related Opportunities for Therapeutic Advances

Loza, Liza C.; Doering, Tamara L.

doi:10.1016/b978-0-12-819475-1.00079-1

Cited by 4 publications

(4 citation statements)

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“…We have come a long way in the 30 years since June Kwon-Chung and her colleagues identified the first capsule gene and demonstrated that capsule is a virulence factor (Figure 3). We now recognize hundreds of genes that influence capsule [46][47][48] and have defined multiple relevant enzymatic and regulatory pathways. The enormous impact of Dr. Kwon-Chung's early work on this field has been sustained in the decades since and is likely to extend into the future, as studies continue to reveal the functions of capsule genes and their crucial roles in C. neoformans biology.…”

Section: Final Thoughtsmentioning

confidence: 99%

A Quick reCAP: Discovering Cryptococcus neoformans Capsule Mutants

Boodwa-Ko,

Doering

2024

JoF

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Cryptococcus neoformans is an opportunistic fungal pathogen that can cause severe meningoencephalitis in immunocompromised hosts and is a leading cause of death in HIV/AIDS patients. This pathogenic yeast is surrounded by a polysaccharide capsule that is critical for virulence and plays important roles in host-pathogen interactions. Understanding capsule biosynthesis is therefore key to defining the biology of C. neoformans and potentially discovering novel therapeutic targets. By exploiting methods to identify mutants deficient in capsule, June Kwon-Chung and other investigators have discovered numerous genes involved in capsule biosynthesis and regulation. Successful approaches have incorporated combinations of techniques including mutagenesis and systematic gene deletion; complementation and genetic screens; morphological examination, physical separation, and antibody binding; and computational modeling based on gene expression analysis. In this review, we discuss these methods and how they have been used to identify capsule mutants.

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Section: Final Thoughtsmentioning

confidence: 99%

A Quick reCAP: Discovering Cryptococcus neoformans Capsule Mutants

Boodwa-Ko,

Doering

2024

JoF

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“…They may physically protect the invading pathogen, mediate cell adherence or protein interactions, transmit signaling information, serve as decoys, or alter the environment to the benefit of the invader, as when biofilm production reduces the efficacy of antibiotics or efficiency of host clearance. Tamara Doering presented the opportunistic eukaryote Cryptococcus neoformans as an example of a pathogen whose glycans are critical for the development of disease (Loza and Doering, 2021). This yeast, which is responsible for roughly 200,000 deaths from meningitis each year, elaborates an extracellular capsule that is composed of large (up to millions of daltons) polysaccharides and can comprise >75% of the pathogen volume.…”

Section: Glycans In Host-pathogen Recognition and Diseasementioning

confidence: 99%

The Crossroads of Glycoscience, Infection, and Immunology

et al. 2021

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Advances in experimental capabilities in the glycosciences offer expanding opportunities for discovery in the broad areas of immunology and microbiology. These two disciplines overlap when microbial infection stimulates host immune responses and glycan structures are central in the processes that occur during all such encounters. Microbial glycans mediate host-pathogen interactions by acting as surface receptors or ligands, functioning as virulence factors, impeding host immune responses, or playing other roles in the struggle between host and microbe. In the context of the host, glycosylation drives cell–cell interactions that initiate and regulate the host response and modulates the effects of antibodies and soluble immune mediators. This perspective reports on a workshop organized jointly by the National Institute of Allergy and Infectious Diseases and the National Institute of Dental and Craniofacial Research in May 2020. The conference addressed the use of emerging glycoscience tools and resources to advance investigation of glycans and their roles in microbe-host interactions, immune-mediated diseases, and immune cell recognition and function. Future discoveries in these areas will increase fundamental scientific understanding and have the potential to improve diagnosis and treatment of infections and immune dysregulation.

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“…Like other fungi, C. neoformans is protected by a multilayer cell wall, which is composed of a meshwork of chitin, chitosan, alpha and beta glucans, and mannoproteins ( 6 ). This flexible and dynamic structure responds to and protects the cell from environmental stresses, while accommodating morphogenesis.…”

Section: Introductionmentioning

confidence: 99%