Biology subjects

Ankur, A.

Publications and source records attributed to Ankur, A..

5 recordsLinked to original sources

bioRxiv2026

Distinguishing Polymer Turnover from De Novo Biosynthesis Reveals Dynamic Cell Wall Remodeling During Aspergillus fumigatus Conidial Germination

Dynamic remodeling of extracellular matrices underlies development, environmental adaptation, and host-pathogen interactions, yet distinguishing polymer turnover from de novo biosynthesis in intact cells remains a major challenge. Here, we combined high-resolution solid-state NMR with selective 13C-labeling strategies to distinguish pre-existing cell-wall polymers from newly synthesized polysaccharides during Aspergillus fumigatus conidial germination. Germination was accompanied by substantial remodeling of the rigid cell wall, characterized by decreased {beta}-1,3-glucan and increased chitin and -1,3-glucan, whereas the mobile wall fraction remained comparatively stable except for the emergence of galactosaminogalactan. Surprisingly, {beta}-1,3-glucan turnover proceeded independently of the major {beta}-1,3-glucanases encoded by the A. fumigatus genome and was dispensable for germination. Instead, isotope-labeling experiments revealed that newly assimilated carbon is preferentially directed toward -1,3-glucan biosynthesis, whereas deletion of the -1,3-glucan synthase genes triggered compensatory accumulation of chitin and {beta}-1,3-glucan. These results reveal a compartmentalized cell-wall remodeling program that coordinates selective turnover with de novo polysaccharide synthesis during fungal germination and establish isotope-edited solid-state NMR as a general approach for distinguishing inherited from newly synthesized polymers in complex carbohydrate matrices.

molecular biology↗

bioRxiv2026

Dynamic Reprogramming of Fungal Cell Walls Underlies Germination and Immune Exposure in Zygomycetous Fungal Pathogens

Fungal germination is a critical developmental transition that underlies environmental adaptation and pathogenicity, yet how the cell wall is molecularly reprogrammed during this process remains poorly understood. Here we show that germination of Rhizopus delemar involves a developmentally programmed transition from a {beta}-1,3-glucan-rich dormant scaffold to a chitin-chitosan-dominated polarized wall. Using solid-state nuclear magnetic resonance spectroscopy and cytochemistry approaches, we show that resting conidia contains a rigid {beta}-1,3-glucan- and chitosan-rich core beneath a persistent melanin layer. During swelling, this architecture is largely maintained, but germ tube emergence triggers complete shutdown of {beta}-1,3-glucan synthesis and extensive chitin-chitosan enrichment. Distinct chitosan polymorphs are selectively enriched, while mobile polysaccharides are progressively incorporated into the rigid scaffold. This remodeling enhances neutrophil recognition of swollen and germinating conidia. Our study reveals a molecular mechanism linking fungal morphogenesis, cell wall remodeling, and morphotype-specific immune exposure during mucormycosis.

biochemistry↗

bioRxiv2026

Molecular Architecture of Cryptococcus Cell Walls Reveals Species-Specific Chitosan-Dependent Remodeling

Cryptococcus neoformans and Cryptococcus gattii are fungal pathogens that cause life-threatening infections, including cryptococcal meningitis. A distinctive feature of the cryptococcal cell wall is the extensive deacetylation of chitin to chitosan, a modification that is essential for virulence but whose structural role in cell-wall organization remains poorly understood. Here, we analyzed the cell walls of wild-type strains of both species and their avirulent chitosan-deficient mutants, which serve as vaccine candidates. Loss of chitosan disrupted cell morphology and altered cell-wall ultrastructure, with more pronounced defects in C. neoformans. Solid-state NMR revealed that aggregated -1,3-glucans form the principal rigid domain of the cell wall in both species and are closely associated with chitin microfibrils, whereas surrounding {beta}-glucans and mannoproteins constitute a more dynamic matrix. Chitosan modulates hydration and flexibility, and its loss increases chitin exposure and triggers species-specific remodeling of the polysaccharide network. In C. neoformans, chitosan depletion increased -1,3-glucan content and reduced {beta}-glucan levels, whereas C. gattii selectively lost one -1,3-glucan subtype while maintaining {beta}-glucan levels. Although capsule production remained intact, chitosan deficiency altered glucuronoxylomannan linkage patterns and mannoprotein composition. These findings reveal how chitosan organizes cryptococcal cell-wall architecture and highlight distinct structural adaptation strategies among pathogenic Cryptococcus species.

biochemistry↗

bioRxiv2026

α-1,3-Glucan-Driven Remodeling of the Conidial Cell Wall in an Aspergillus fumigatus Vaccine Strain Alters Innate Immune Recognition

Aspergillus fumigatus is a major cause of invasive aspergillosis in immunocompromised patients, where current antifungal therapies are limited by toxicity, drug resistance, and lack of durable protection, and no vaccines are available. A mutant lacking the sterylglucosidase-encoding gene (sglA) has emerged as a candidate that induces protective immune responses, but the structural basis for this phenotype remains unclear. Here, we use cellular solid-state NMR spectroscopy to compare the organization of the conidial cell wall in {Delta}sglA and its wild-type counterpart. The {Delta}sglA conidial cell wall displays extensive remodeling, including increased -1,3-glucan content and structural polymorphism, strengthened interactions with {beta}-glucans, reduced hydration, and restricted molecular motion, together consolidating a more rigid scaffold with limited {beta}-glucan accessibility. These structural changes are associated with altered neutrophil responses and a shift in innate immune signaling. This work links cell-wall reorganization to altered immune recognition in this vaccine candidate, with implications for future immunotherapeutic strategies. TEASERMolecular-level Insights from a fungal vaccine candidate show how cell-wall remodeling could affect immune response.

biochemistry↗

bioRxiv2025

Polymorphic α-Glucans as Structural Scaffolds in Cryptococcus Cell Walls for Chitin, Capsule, and Melanin: Insights from 13C and 1H Solid-State NMR

Cryptococcus species are major fungal pathogens responsible for life-threatening infections in approximately a million individuals globally each year, with alarmingly high mortality rates. These fungi are distinguished by a distinctive cell wall architecture further reinforced by two virulence-associated layers, melanin and capsule, rendering them insensitive to antifungal agents targeting the cell wall, such as echinocandins. The molecular interplay between these three biomolecular layers remains poorly understood. Here we employ solid-state NMR spectroscopy to examine intact cells of both wild-type and capsule-deficient strains of C. neoformans, along with its melanized cells. High-resolution 13C and 1H data revealed five distinct structural forms of -1,3-glucans that play versatile roles in forming the rigid cell wall scaffold by interacting with chitin microfibrils and chitosan, and in stabilizing the mobile matrix by associating with {beta}-1,6-glucan and a small fraction of {beta}-1,3-glucan. Two primary forms of -1,3-glucans were distributed throughout the cell wall, hosting melanin deposition in the inner domain and capsule attachment on the cell surface. These findings offer a paradigm shift in understanding the cryptococcal cell wall and its interaction with two key virulence factors on opposite sides, raising critical biochemical questions that could inform the development of more effective antifungal treatments for cryptococcosis.

biochemistry↗