ChemInform Abstract: Novel Nikkomycin Analogues: Inhibitors of the Fungal Cell Wall Biosynthesis Enzyme Chitin Synthase.

ChemInform ◽  
2000 ◽  
Vol 31 (41) ◽  
pp. no-no
Author(s):  
Kikoh Obi ◽  
Jun-ichiro Uda ◽  
Kazuhiko Iwase ◽  
Osamu Sugimoto ◽  
Hiroyuki Ebisu ◽  
...  
Keyword(s):  
Cell Wall ◽  
Fungal Cell Wall ◽  
Chitin Synthase ◽  
Cell Wall Biosynthesis ◽  
Fungal Cell

Novel nikkomycin analogues: inhibitors of the fungal cell wall biosynthesis enzyme chitin synthase

2000 ◽  
Vol 10 (13) ◽  
pp. 1451-1454 ◽  
Author(s):  
Kikoh Obi ◽  
Jun-ichiro Uda ◽  
Kazuhiko Iwase ◽  
Osamu Sugimoto ◽  
Hiroyuki Ebisu ◽  
...  
Keyword(s):  
Cell Wall ◽  
Fungal Cell Wall ◽  
Chitin Synthase ◽  
Cell Wall Biosynthesis ◽  
Fungal Cell

scholarly journals Length Specificity and Polymerization Mechanism of (1,3)-β-d-Glucan Synthase in Fungal Cell Wall Biosynthesis

Biochemistry ◽  
2020 ◽  
Vol 59 (5) ◽  
pp. 682-693 ◽  
Author(s):  
Abhishek Chhetri ◽  
Anna Loksztejn ◽  
Hai Nguyen ◽  
Kaila M. Pianalto ◽  
Mi Jung Kim ◽  
...  
Keyword(s):  
Cell Wall ◽  
Fungal Cell Wall ◽  
Cell Wall Biosynthesis ◽  
Fungal Cell ◽  
Glucan Synthase ◽  
Polymerization Mechanism

scholarly journals Cryptococcus neoformans Chitin Synthase 3 (Chs3) Plays a Critical Role in Dampening Host Inflammatory Responses

2019 ◽  
Author(s):  
Camaron R. Hole ◽  
Woei C. Lam ◽  
Rajendra Upadhya ◽  
Jennifer K. Lodge
Keyword(s):  
Immune Response ◽  
Cell Wall ◽  
Cryptococcus Neoformans ◽  
Inflammatory Responses ◽  
Critical Role ◽  
Pathogenic Fungi ◽  
Fungal Cell Wall ◽  
Chitin Synthase ◽  
Aids Patients ◽  
Fungal Cell

ABSTRACTCryptococcus neoformans infections are significant causes of morbidity and mortality among AIDS patients and the third most common invasive fungal infection in organ transplant recipients. One of the main interfaces between the fungus and the host is the fungal cell wall. The cryptococcal cell wall is unusual among human pathogenic fungi in that the chitin is predominantly deacetylated to chitosan. Chitosan deficient strains of C. neoformans were found to be avirulent and rapidly cleared from the murine lung. Moreover, infection with a chitosan deficient C. neoformans lacking three chitin deacetylases (cda1Δ2Δ3Δ) was found to confer protective immunity to a subsequent challenge with a virulent wild type counterpart. In addition to the chitin deacetylases, it was previously shown that chitin synthase 3 (Chs3) is also essential for chitin deacetylase mediated formation of chitosan. Mice inoculated with chs3Δ at a dose previously shown to induce protection with cda1Δ2Δ3Δ die within 36 hours after installation of the organism. Mortality was not dependent on viable fungi as mice inoculated with heat-killed preparation of chs3Δ died at the same rate as mice inoculated with live chs3Δ, suggesting the rapid onset of death was host mediated likely caused by an over exuberant immune response. Histology, cytokine profiling, and flow cytometry indicates a massive neutrophil influx in the mice inoculated with chs3Δ. Mice depleted of neutrophils survived chs3Δ inoculation indicating that death was neutrophil mediated. Altogether, these studies lead us to conclude that Chs3, along with chitosan, plays critical roles in dampening cryptococcal induced host inflammatory responses.IMPORTANCECryptococcus neoformans is the most common disseminated fungal pathogen in AIDS patients, resulting in ∼200,000 deaths each year. There is a pressing need for new treatments for this infection, as current antifungal therapy is hampered by toxicity and/or the inability of the host’s immune system to aid in resolution of the disease. An ideal target for new therapies is the fungal cell wall. The cryptococcal cell wall is different than many other pathogenic fungi in that it contains chitosan. Strains that have decreased chitosan are less pathogenic and strains that are deficient in chitosan are avirulent and can induce protective responses. In this study we investigated the host responses to chs3Δ, a chitosan-deficient strain, and found mice inoculated with chs3Δ all died within 36 hours and death was associated with an aberrant hyperinflammatory immune response driven by neutrophils, indicating that chitosan is critical in modulating the immune response to Cryptococcus.

scholarly journals Protein Kinase A and High-Osmolarity Glycerol Response Pathways Cooperatively Control Cell Wall Carbohydrate Mobilization inAspergillus fumigatus

mBio ◽  
2018 ◽  
Vol 9 (6) ◽  
Author(s):  
Leandro José de Assis ◽  
Adriana Manfiolli ◽  
Eliciane Mattos ◽  
João H. T. Marilhano Fabri ◽  
Iran Malavazi ◽  
...  
Keyword(s):  
Cell Wall ◽  
Protein Kinase ◽  
Glycogen Synthesis ◽  
Fungal Cell Wall ◽  
Cell Wall Biosynthesis ◽  
Fungal Cell ◽  
Content Type ◽  
High Osmolarity ◽  
High Osmolarity Glycerol ◽  
Kinase A

ABSTRACTAspergillus fumigatusmitogen-activated protein kinases (MAPKs) are involved in maintaining the normal morphology of the cell wall and providing resistance against cell wall-damaging agents. Upon cell wall stress, cell wall-related sugars need to be synthesized from carbohydrate storage compounds. Here we show that this process is dependent on cAMP-dependent protein kinase A (PKA) activity and regulated by the high-osmolarity glycerol response (HOG) MAPKs SakA and MpkC. These protein kinases are necessary for normal accumulation/degradation of trehalose and glycogen, and the lack of these genes reduces glucose uptake and glycogen synthesis. Alterations in glycogen synthesis were observed for thesakAandmpkCdeletion mutants, which also displayed alterations in carbohydrate exposure on the cell wall. Carbohydrate mobilization is controlled by SakA interaction with PkaC1 and PkaR, suggesting a putative mechanism where the PkaR regulatory subunit leaves the complex and releases the SakA-PkaC1 complex for activation of enzymes involved in carbohydrate mobilization. This work reveals the communication between the HOG and PKA pathways for carbohydrate mobilization for cell wall construction.IMPORTANCEAspergillus fumigatusis an opportunistic human pathogen causing allergic reactions or systemic infections such as invasive pulmonary aspergillosis, especially in immunocompromised patients. The fungal cell wall is the main component responsible for recognition by the immune system, due to the specific composition of polysaccharide carbohydrates exposed on the surface of the fungal cell wall called pathogen-associated molecular patterns (PAMPs). Key enzymes in the fungal cell wall biosynthesis are a good target for fungal drug development. This report elucidates the cooperation between the HOG and PKA pathways in the mobilization of carbohydrates for fungal cell wall biosynthesis. We suggest that the reduced mobilization of simple sugars causes defects in the structure of the fungal cell wall. In summary, we propose that SakA is important for PKA activity, therefore regulating the availability and mobilization of monosaccharides for fungal cell wall biosynthesis during cell wall damage and the osmotic stress response.

Fungal cell wall biosynthesis: a view on biodiversity in fungi and application of ‘-omics’

Yeast ◽  
2007 ◽  
Vol 24 (4) ◽  
pp. 217-219 ◽  
Author(s):  
Sabine Strahl ◽  
Jürgen J. Heinisch
Keyword(s):  
Cell Wall ◽  
Fungal Cell Wall ◽  
Cell Wall Biosynthesis ◽  
Fungal Cell

Chitin synthase gene FgCHS8 affects virulence and fungal cell wall sensitivity to environmental stress in Fusarium graminearum

2016 ◽  
Vol 120 (5) ◽  
pp. 764-774 ◽  
Author(s):  
Ya-Zhou Zhang ◽  
Qing Chen ◽  
Cai-Hong Liu ◽  
Yu-Bin Liu ◽  
Pan Yi ◽  
...  
Keyword(s):  
Cell Wall ◽  
Environmental Stress ◽  
Fusarium Graminearum ◽  
Fungal Cell Wall ◽  
Chitin Synthase ◽  
Fungal Cell
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