N-Acetylglucosamine Regulates Morphogenesis and Virulence Pathways in Fungi

Abstract

N-acetylglucosamine (GlcNAc) is being increasingly recognized for its ability to stimulate cell signaling. This amino sugar is best known as a component of cell wall peptidoglycan in bacteria, cell wall chitin in fungi and parasites, exoskeletons of arthropods, and the extracellular matrix of animal cells. In addition to these structural roles, GlcNAc is now known to stimulate morphological and stress responses in a wide range of organisms. In fungi, the model organisms Saccharomyces cerevisiae and Schizosaccharomyces pombe lack the ability to respond to GlcNAc or catabolize it, so studies with the human pathogen Candida albicans have been providing new insights into the ability of GlcNAc to stimulate cellular responses. GlcNAc potently induces C. albicans to transition from budding to filamentous hyphal growth. It also promotes an epigenetic switch from White to Opaque cells, which differ in morphology, metabolism, and virulence properties. These studies have led to new discoveries, such as the identification of the first eukaryotic GlcNAc transporter. Other results have shown that GlcNAc can induce signaling in C. albicans in two ways. One is to act as a signaling molecule independent of its catabolism, and the other is that its catabolism can cause the alkalinization of the extracellular environment, which provides an additional stimulus to form hyphae. GlcNAc also induces the expression of virulence genes in the C. albicans, indicating it can influence pathogenesis. Therefore, this review will describe the recent advances in understanding the role of GlcNAc signaling pathways in regulating C. albicans morphogenesis and virulence.

Pathogenesis and Clinical Relevance of Candida Biofilms in Vulvovaginal Candidiasis

“…RON1 deletion leads to growth defects when grown in GlcNAc media and hypha induction. To avoid this, a new short cross-linked palindromic/CRISPR repeat associated with Cas9 has been used for gene deletions (Min et al, 2019). Tang et al (2019) demonstrated that the majority of C. albicans strains are capable of undergoing the phenomenon of phenotypic switch, which is associated with the manifestation of phenotypic changes at high frequency and a consequence of the action of numerous environmental factors.…”

“…According to Min et al (2019) , N -acetylglucosamine (GlcNAc) potently induces the transition of C. albicans from budding to filamentous hypha growth. It also stimulates an epigenetic change that converts the white cells to opaque cells, which vary in morphology, metabolism, and virulence properties.…”

N-acetylglucosamine Signaling: Transcriptional Dynamics of a Novel Sugar Sensing Cascade in a Model Pathogenic Yeast, Candida albicans

“…N-acetylglucosamine (GlcNAc) is an often encountered carbon source in nature, being a component of peptidoglycan of the bacterial cell wall, fungal chitin, insect exoskeleton, and mammalian extra cellular matrix [ 20 , 21 ]. Apart from structural functions, its role in stimulating cellular signaling in pathogenic yeast C. albicans makes it an attractive sugar signaling molecule.…”

“…GlcNAc regulates multifaceted cellular functions that make it very interesting to understand the signaling mechanisms [ 21 , 48 ].…”

N-Acetylglucosamine (GlcNAc) Sensing, Utilization, and Functions in Candida albicans

“…It is also found in the extracellular matrix of bacterial biofilms and in the extracellular matrix glycosaminoglycans of animal cells [ 1 ]. GlcNAc is a nutrient source for many microorganisms and also plays critical roles in signaling for both bacterial and mammalian cells [ 1 , 2 , 3 ]. It regulates a variety of biological processes including morphological transitions, virulence, response to oxidative stresses and antifungal agents, and cell death in several fungal species such as Candida albicans [ 1 , 4 , 5 , 6 , 7 ], Candida tropicalis [ 8 , 9 , 10 ], Yarrowia lipolytica [ 11 ], and Histoplasma capsulatum [ 12 ].…”