A fungal lytic polysaccharide monooxygenase is required for cell wall integrity, thermotolerance, and virulence of the fungal human pathogenCryptococcus neoformans

Abstract

Fungi often adapt to environmental stress by altering their size, shape, or rate of cell division. These morphological changes require reorganization of the cell wall, a structural feature external to the cell membrane composed of highly interconnected polysaccharides and glycoproteins. Lytic polysaccharide monooxygenases (LPMOs) are copper-dependent enzymes that are typically secreted into the extracellular space to catalyze initial oxidative steps in the degradation of complex biopolymers such as chitin and cellulose. However, their roles in modifying endogenous microbial carbohydrates are poorly characterized. The CEL1 gene in the human fungal pathogen Cryptococcus neoformans (Cn) is predicted by sequence homology to encode an LPMO of the AA9 enzyme family. The CEL1 gene is induced by host physiological pH and temperature, and it is primarily localized to the fungal cell wall. Targeted mutation of the CEL1 gene revealed that it is required for the expression of stress response phenotypes, including thermotolerance, cell wall integrity, and efficient cell cycle progression. Accordingly, a cel1Δ deletion mutant was avirulent in two models of C. neoformans infection. Therefore, in contrast to LPMO activity in other microorganisms that primarily targets exogenous polysaccharides, these data suggest that CnCel1 promotes intrinsic fungal cell wall remodeling events required for efficient adaptation to the host environment.

Differential expression and gene correlation analyses reveal core CAZymes in Fusarium oxysporum f.sp. lycopersici exposed to mutagen and heat stress

“…The core gene accessions that belonged to GH families (GH3, GH15, GH16, GH17, GH18, GH45, GH128, GH125, and GH132) with assisting LPMOs (AA7, AA9, and AA11) were found to be downregulated under both the perturbations that were involved in glucanase/glucosidase, mannosidase, and chitinase activities. The role of LPMO in cell wall integrity was found evident in a human pathogenic yeast recently (Probst et al., 2023), and the coordinated secretion of glucanase/glucosidase, mannosidase enzymes was previously revealed in a Trichoderma species during fungal–fungal interaction (Monteiro et al., 2010). Further, these cell wall‐modifying enzymes such as endo‐ and exo‐β‐glucanase play a crucial role during conidiation as well as in remodelling of the fungal cell wall such as hyphal branching and mycelial growth by softening of the existing cell wall (Mouyna et al., 2013, 2016).…”

The disordered C-terminal tail of fungal LPMOs from phytopathogens mediates protein dimerization and impacts plant penetration

“…LPMO biological functions only start to be unveiled (9). A few recent reports have notably pinpointed the involvement of LPMOs in the mechanism of a couple of fungal pathogens, notably in Cryptococcus neoformans and Magnaporthe oryzae (15,54,55). Herein, considering that i) CoAA9A is a cellulolytic LPMO, ii) CoAA9A is secreted as a dimer during appressorium development, and iii) Δaa9a deletion strains displayed impaired penetration capabilities during infection, we hypothesize that CoAA9A facilitates plant cell wall disruption during the formation of the penetration hyphae.…”

Dual RNA sequencing during Trichoderma harzianum–Phytophthora capsici interaction reveals multiple biological processes involved in the inhibition and highlights the cell wall as a potential target

“…As is well known, polysaccharides are essential components of the cell walls of various organisms, including plants, fungi, oomycetes, and bacteria. [42][43][44][45] However, the composition and quantity of polysaccharides in the cell wall can vary significantly between different species. For instance, chitin synthesized by chitin synthases is a prominent carbohydrate component of the fungal cell wall.…”