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Differential cell wall remodeling of two chitin synthase deletants Δchs3A and Δchs3B in the pathogenic yeast Candida glabrata.

It is known that cell wall remodeling and the salvaging pathway act to compensate for an impaired or a damaged cell wall. Lately, it has been indicated that this mechanism is partly required for resistance to the glucan synthesis inhibitor echinocandin. While cell wall remodeling has been described in mutants of glucan or mannan synthesis, it has not yet been reported in a chitin synthesis mutant. Here, we describe a novel cell wall remodeling and salvaging pathway in chitin synthesis mutants, Δchs3A and Δchs3B, of the pathogenic yeast Candida glabrata. Electron microscopic analysis revealed a

A Trichoderma milRNA cross-species targeting chitin synthases genes is delivered by carbon nanomaterials to suppress Botrytis cinerea.

Botrytis cinerea is a globally destructive plant pathogen that threatens major agricultural crops. Although biocontrol agents are widely use … les, enabling cross-species RNA interference (RNAi). Once inside B. cinerea, Tri-milR29 targets the chitin synthase genes BcCHS7 and BcCHS6, thereby impairing fungal growth and reducing its pathogenicity. This cross-species miRNA phenomenon significantly enhanced the antifungal and disease-suppressing efficacy of T. breve against B. cinerea. Moreover, to optimize …

Candida albicans strains deficient in CHS7, a key regulator of chitin synthase III, exhibit morphogenetic alterations and attenuated virulence.

Chitin is a structural polysaccharide present in most fungal cell walls, whose synthesis depends on a family of enzymic activities named chitin synthases (CSs). The specific role of each of them, as well as of their regulatory proteins, in cell morphogenesis and virulence is not well understood. Here, it is shown that most chitin synthesis in Candida albicans, one of the fungi most commonly isolated from opportunistic mycoses and infections, depends on CHS7. Thus, C. albicans chs7Delta null mutants showed reduced levels of chitin and CS activity, and were resistant to Calcofluor. Despite the s…

Identification of GIG1, a GlcNAc-induced gene in Candida albicans needed for normal sensitivity to the chitin synthase inhibitor nikkomycin Z.

The amino sugar N-acetylglucosamine (GlcNAc) is known to be an important structural component of cells from bacteria to humans, but its role … ccurs. Significantly, a gig1Δ mutant displayed increased resistance to nikkomycin Z, which inhibits chitin synthase from converting UDP-GlcNAc into cell wall chitin. Gig1 is highly conserved in fungi, especially those that contain GlcNAc catabolic genes. These results implicate Gig1 in GlcNAc metabolism.

Controlled delivery of nikkomycin by PEG coated PLGA nanoparticles inhibits chitin synthase to prevent growth of Aspergillus flavus and Aspergillus fumigatus.

Aspergillosis is one of the most common fungal infections that can threaten individuals with immune compromised condition. Due to the increasing resistance of pathogens to the existing antifungal drugs, it is difficult to tackle such disease conditions. Whereas, nikkomycin is an emerging safe and effective antifungal drug which causes fungal cell wall disruption by inhibiting chitin synthase. Hence, the study aims at the development of nikkomycin loaded PEG coated PLGA nanoparticles for its increased antifungal efficiency and inhibiting Aspergillus infections. The P-PLGA-Nik NPs were synthesiz…

Ethylenediaminetetraacetic Acid Disodium Salt Acts as an Antifungal Candidate Molecule against Fusarium graminearum by Inhibiting DON Biosynthesis and Chitin Synthase Activity.

Fusarium fungi are the cause of an array of devastating diseases affecting yield losses and accumulating mycotoxins. Fungicides can be explo … ter amending cultures with EDTANa2 and the expression of several TRI genes significantly decreased. Chitin synthases of Fusarium were Mn2+-containing enzymes that were strongly inhibited by Mn2+ deficiency. EDTANa2 inhibited chitin synthesis and destroyed the cell wall and cytomembrane integrity of Fusarium, mainly via the chelation of Mn2+ by EDTANa2, and thus l …

The Glucan-Remodeling Enzyme Phr1p and the Chitin Synthase Chs1p Cooperate to Maintain Proper Nuclear Segregation and Cell Integrity in Candida albicans.

GH72 family of β-(1,3)-glucanosyltransferases is unique to fungi and is required for cell wall biogenesis, morphogenesis, virulence, and in … hr1p-GFP still concentrated along the thin line of the primary septum formed by chitin deposited by chitin synthase I (whose catalytic subunit is Chs1p) suggesting that it plays a role during formation of the secondary septa. RO-09-3143, a highly specific inhibitor of Chs1p activity, inhibits septum formation and blocks cell division. However, alternative septa a …

Novel spiro[pyrrolidine-2,3'-quinoline]-2'-one derivatives containing piperazine fragment as potential chitin synthase inhibitors and antifungal agents: Design, synthesis and biological evaluation.

A series of spiro[pyrrolidine-2,3'-quinoline]-2'-one derivatives were designed and synthesized for the discovery of novel antifungal drugs. The bioactivities of all derivatives were screened by evaluating their inhibitory effects against chitin synthase (CHS) and antimicrobial activities in vitro. Enzyme inhibition experiments showed that all the synthesized compounds inhibited the chitin synthase. Compounds 4d, 4k, 4n and 4o showed inhibitory effects against CHS with IC50 values which were close to that of the control drug (polyoxin B). The results of enzyme kinetics experiment showed that th…

Куркумин влияет на синтез хитина в Aedes aegypti: вычислительное и экспериментальное исследование.

На протяжении всей истории трансмиссивые заболевания неизменно создавали серьезные проблемы для здоровья человека. В рамках стратегий борьбы с переносчиками химических инсектицидов с момента их создания широко применяются. Тем не менее их эффективность постоянно подрывается устойчивым ростом резистентности к инсектицидам среди этих переносчиков. Спрос на более надежные, эффективные и рентабельные природные инсектициды как таковые становится все более насущным. Одним из многообещающих направлений исследований является шитин, который является важнейшим структурным компонентом экзоскелетов комаро

Совпадение в аннотации оригинала
Throughout history, vector-borne diseases have consistently posed significant challenges to human health. Among the strategies for vector co … process known as ecdysis. Crucially, the production of chitin is facilitated by an enzyme known as chitin synthase, making it an attractive target for potential novel insecticides. Our recent study delved into the impacts of curcumin, a natural derivative of turmeric, on chitin synthesis and larval development in Aedes aegypti, a mosquito species known to transm …

A septin-based hierarchy of proteins required for localized deposition of chitin in the Saccharomyces cerevisiae cell wall.

Just before bud emergence, a Saccharomyces cerevisiae cell forms a ring of chitin in its cell wall; this ring remains at the base of the bud as the bud grows and ultimately forms part of the bud scar marking the division site on the mother cell. The chitin ring seems to be formed largely or entirely by chitin synthase III, one of the three known chitin synthases in S. cerevisiae. The chitin ring does not form normally in temperature-sensitive mutants defective in any of four septins, a family of proteins that are constituents of the "neck filaments" that lie immediately subjacent to the plasma…

Caspofungin Treatment of Aspergillus fumigatus Results in ChsG-Dependent Upregulation of Chitin Synthesis and the Formation of Chitin-Rich Microcolonies.

Treatment of Aspergillus fumigatus with echinocandins such as caspofungin inhibits the synthesis of cell wall β-1,3-glucan, which triggers a compensatory stimulation of chitin synthesis. Activation of chitin synthesis can occur in response to sub-MICs of caspofungin and to CaCl2 and calcofluor white (CFW), agonists of the protein kinase C (PKC), and Ca(2+)-calcineurin signaling pathways. A. fumigatus mutants with the chs gene (encoding chitin synthase) deleted (ΔAfchs) were tested for their response to these agonists to determine the chitin synthase enzymes that were required for the compensat…

Modulating chitin synthesis in marine algae with iminosugars obtained by SmI2 and FeCl3-mediated diastereoselective carbonyl ene reaction.

Strategies for synthesizing polyhydroxylated piperidines such as iminosugars have received broad attention. These substances are known to interact with carbohydrate related enzymes, glycosidases and glycosyltransferases, to which also the large enzyme families of chitin synthases and cellulose synthases belong. Many chemical and biological aspects of chitin synthases remain unexplored due to the fact that modulating substances are hardly available or expensive. Starting from enantiopure D- and L-amino acids, a series of iminosugars was prepared by a Lewis acid-catalyzed cyclization of amino ac…

Structural basis for directional chitin biosynthesis.

Chitin, the most abundant aminopolysaccharide in nature, is an extracellular polymer consisting of N-acetylglucosamine (GlcNAc) units1. The key reactions of chitin biosynthesis are catalysed by chitin synthase2-4, a membrane-integrated glycosyltransferase that transfers GlcNAc from UDP-GlcNAc to a growing chitin chain. However, the precise mechanism of this process has yet to be elucidated. Here we report five cryo-electron microscopy structures of a chitin synthase from the devastating soybean root rot pathogenic oomycete Phytophthora sojae (PsChs1). They represent the apo, GlcNAc-bound, nasc…

Chitin is only a minor component of the peritrophic matrix from larvae of Lucilia cuprina.

The gut of most insects is lined with a peritrophic matrix that facilitates the digestive process and protects insects from invasion by micr … content in a biological sample, is only 7.2% of the weight of the matrix. Larvae fed on the potent chitin synthase inhibitor polyoxin D or the chitin-binding agent Calcofluor White, showed strong concentration-dependent inhibition of larval weight and survival but no discernible effects on the matrix structure. A bacterial endochitinase fed to larvae had no effe …

Molecular architecture of chitin and chitosan-dominated cell walls in zygomycetous fungal pathogens by solid-state NMR.

Zygomycetous fungal infections pose an emerging medical threat among individuals with compromised immunity and metabolic abnormalities. Our … ains galactan- and mannan-based polysaccharides, along with polymeric α-fucoses. Treatment with the chitin synthase inhibitor nikkomycin removes the β-glucan-chitin/chitosan complex, leaving the other chitin and chitosan allomorphs untouched while simultaneously thickening and rigidifying the cell wall. These findings shed light on the organization of Mucorales c …

Curvature of the Drosophila corneal lens depends on localized chitin secretion.

The Drosophila corneal lens is an apical extracellular matrix structure with a biconvex shape that enables it to focus light onto the underlying photoreceptors. Here, we investigated how this shape is influenced by the source of one of its major components, the polysaccharide chitin. Knocking down the chitin synthase Krotzkopf verkehrt strongly reduced the thickness and curvature of the corneal lens. Conversely, enhancing chitin export by overexpressing Rebuf expanded and distorted the corneal lens. We found that the cone and primary pigment cells in the center of each ommatidium produce most …

Evidence of chitin in the ampullae of Lorenzini of chondrichthyan fishes.

We previously reported that the polysaccharide chitin, a key component of arthropod exoskeletons and fungal cell walls, is endogenously produced by fishes and amphibians in spite of the widely held view that it was not synthesized by vertebrates [1]. Genes encoding chitin synthase enzymes were found in the genomes of a number of fishes and amphibians and shown to be correspondingly expressed at the sites where chitin was localized [1,2]. In this report, we present evidence suggesting that chitin is prevalent within the specialized electrosensory organs of cartilaginous fishes (Chondrichthyes).…

Easy-to-use imaging-cytometry assay to analyze chitin patterns in yeasts.

BACKGROUND & AIM: Pathogenic fungi are a major threat to public health, and fungal infections are becoming increasingly common and treatment resistant. Chitin, a component of the fungal cell wall, modifies host immunity and contributes to antifungal resistance. Moreover, chitin content is regulated by chitin synthases and chitinases. However, the specific roles and mechanisms remain unclear. In this study, we developed a cytometric imaging assay to quantify chitin content and identify the distribution of chitin in the yeast cell wall. METHODS: The Candida albicans SC5314 and Nakaseomyces glab…

In vivo hyaluronan synthesis upon expression of the mammalian hyaluronan synthase gene in Drosophila.

Hyaluronan (HA) is a large linear polymer of repeating disaccharides of glucuronic acid and GlcNAc. Although HA is widely distributed in vertebrate animals, it has not been found in invertebrates, including insect species. Insects utilize chitin, a repeating beta-1,4-linked homopolymer of GlcNAc, as a major component of their exoskeleton. Recent studies illustrate the similarities in the biosynthetic mechanisms of HA and chitin and suggest that HA synthase (HAS) and chitin synthase have evolved from a common ancestral molecule. Although the biochemical properties and in vivo functions of HAS p…

Determination of chitin content in fungal cell wall: an alternative flow cytometric method.

The conventional methods used to evaluate chitin content in fungi, such as biochemical assessment of glucosamine release after acid hydrolys … in were evaluated. Candida albicans clinical isolate SC5314, and isogenic strains with deletions in chitin synthase 3 (chs3Δ/chs3Δ) and genes encoding predicted GlycosylPhosphatidylInositol (GPI)-anchored proteins (pga31Δ/Δ and pga62Δ/Δ), were used as controls. As expected, the wild-type strain displayed a significant higher chitin content (P < 0.001) than chs3Δ/ …