The primary purpose of this study is to evaluate if eating a high fat meal versus not eating any food affects how the study drug (Nikkomycin Z) is absorbed into the body. The second purpose is to gain further information about the safety of Nikkomycin Z in healthy adults.

开始日期2012-07-01

申办/合作机构

University of Arizona

NCT00834184 / Completed临床1期IIT

Phase I, Randomized, Double-blind, Placebo Controlled, Multiple-dose Evaluation of the Safety Tolerance and Pharmacokinetics of Nikkomycin Z in Healthy Subjects

开始日期2008-10-01

申办/合作机构

University of Arizona

NCT00614666 / Terminated临床1/2期IIT

Phase I/II Evaluation of the Safety, Pharmacokinetics, and Preliminary Effectiveness of Nikkomycin Z in the Treatment of Patients With Uncomplicated Coccidioides Pneumonia

The purpose of this study is to determine if nikkomycin Z is safe when administered at different dose levels for 14 days. The study will also determine blood levels and urinary excretion of nikkomycin Z in relation to dose administered. Patients with mild forms of Valley Fever pneumonia will be eligible to participate and will be allocated to receive treatment with nikkomycin Z (various doses) or a placebo. A secondary goal of this study is to evaluate the effectiveness and dose response of nikkomycin Z in an exploratory analysis.

开始日期2007-09-01

申办/合作机构

University of Arizona

100 项与 Chitin synthase 相关的临床结果

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100 项与 Chitin synthase 相关的转化医学

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0 项与 Chitin synthase 相关的专利（医药）

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851

项与 Chitin synthase 相关的文献（医药）

2024-12-01·Applied Microbiology and Biotechnology

Membrane protein Bcsdr2 mediates biofilm integrity, hyphal growth and virulence of Botrytis cinerea

Article

作者: Ge, Beibei ; Shi, Liming ; Li, Hua ; Zhang, Wei ; Zhang, Kecheng ; Cao, Yi ; Rasmey, Abdel-Hamied M

AbstractGrey mould caused by Botrytis cinerea is a devastating disease responsible for large losses to agricultural production, and B. cinerea is a necrotrophic model fungal plant pathogen. Membrane proteins are important targets of fungicides and hotspots in the research and development of fungicide products. Wuyiencin affects the permeability and pathogenicity of B. cinerea, parallel reaction monitoring revealed the association of membrane protein Bcsdr2, and the bacteriostatic mechanism of wuyiencin was elucidated. In the present work, we generated and characterised ΔBcsdr2 deletion and complemented mutant B. cinerea strains. The ΔBcsdr2 deletion mutants exhibited biofilm loss and dissolution, and their functional activity was illustrated by reduced necrotic colonisation on strawberry and grape fruits. Targeted deletion of Bcsdr2 also blocked several phenotypic defects in aspects of mycelial growth, conidiation and virulence. All phenotypic defects were restored by targeted gene complementation. The roles of Bcsdr2 in biofilms and pathogenicity were also supported by quantitative real-time RT-PCR results showing that phosphatidylserine decarboxylase synthesis gene Bcpsd and chitin synthase gene BcCHSVII were downregulated in the early stages of infection for the ΔBcsdr2 strain. The results suggest that Bcsdr2 plays important roles in regulating various cellular processes in B. cinerea.Key points• The mechanism of wuyiencin inhibits B. cinerea is closely associated with membrane proteins.• Wuyiencin can downregulate the expression of the membrane protein Bcsdr2 in B. cinerea.• Bcsdr2 is involved in regulating B. cinerea virulence, growth and development.

2024-12-01·Fungal Genetics and Biology

Putative APSES family transcription factor mbp1 plays an essential role in regulating cell wall synthesis in the agaricomycete Pleurotus ostreatus

Article

作者: Yoshimi, Akira ; Nakazawa, Takehito ; Kojima, Hayase ; Tanaka, Chihiro ; Schiphof, Kim ; Otsuka, Yuitsu ; Honda, Yoichi ; Kawauchi, Moriyuki ; Tsuji, Kenya ; Yano, Shigekazu

The clade A APSES family transcription factors (Mbp1, Swi4, and Swi6) contribute to cell wall synthesis regulation in fungi. Herein, evolutionary relationships among these proteins were clarified by phylogenetic analysis using various ascomycetes and basidiomycetes, and then the detailed function of Mbp1 in cell wall synthesis regulation was analyzed in Pleurotus ostreatus. Our phylogenetic analysis revealed that Mbp1 and Swi6 are widely conserved among various fungi, whereas Swi4 is a protein specific for Saccharomycotina. In P. ostreatus, two putative clade A APSES family transcription factors, protein ID 83192 and 134090, were found and identified as Mbp1 and Swi6, respectively. The mbp1 gene was then disrupted through homologous recombination using P. ostreatus 20b strain (Δku80) as a host to obtain mbp1 disruption strains (Δmbp1). Disruption of mbp1 significantly decreased the growth rate and shortened aerial hyphae, suggesting that Mbp1 is involved in mycelial growth, especially aerial hyphal growth. Furthermore, thinner cell walls, decreased relative percentage of β-glucan, and downregulation of all β-glucan synthase genes were observed in Δmbp1 strains. Therefore, Mbp1 plays an essential role in β-glucan synthesis regulation in P. ostreatus. Disruption of mbp1 also impacted the expression profiles of chitin synthase genes, septum formation, and sensitivity to a chitin synthesis inhibitor, suggesting that Mbp1 also regulates chitin synthesis. In conclusion, Mbp1 is responsible for normal mycelial growth and regulates β-glucan and chitin synthesis in P. ostreatus. To the best of our knowledge, this is the first report on the detailed function of Mbp1 in cell wall synthesis regulation in fungi.

2024-12-01·Molecular Phylogenetics and Evolution

Evolution of chitin-synthase in molluscs and their response to ocean acidification

Article

作者: Cardoso, João C R ; Power, Deborah M. ; Cardoso, João C.R. ; Peng, Maoxiao ; Power, Deborah M

Chitin-synthase (CHS) is found in most eukaryotes and has a complex evolutionary history. Research into CHS has mainly been in the context of biomineralization of mollusc shells an area of high interest due to the consequences of ocean acidification. Exploration of CHS at the genomic level in molluscs, the evolution of isoforms, their tissue distribution, and response to environmental challenges are largely unknown. Exploiting the extensive molecular resources for mollusc species it is revealed that bivalves possess the largest number of CHS genes (12-22) reported to date in eukaryotes. The evolutionary tree constructed at the class level of molluscs indicates four CHS Type II isoforms (A-D) probably existed in the most recent common ancestor, and Type II-A (Type II-A-1/Type II-A-2) and Type II-C (Type II-C-1/Type II-C-2) underwent further differentiation. Non-specific loss of CHS isoforms occurred at the class level, and in some Type II (B-D groups) isoforms the myosin head domain, which is associated with shell formation, was not preserved and highly species-specific tissue expression of CHS isoforms occurred. These observations strongly support the idea of CHS functional diversification with shell biomineralization being one of several important functions. Analysis of transcriptome data uncovered the species-specific potential of CHS isoforms in shell formation and a species-specific response to ocean acidification (OA). The impact of OA was not CHS isoform-dependent although in Mytilus, Type I-B and Type II-D gene expression was down-regulated in both M. galloprovincialis and M. coruscus. In summary, during CHS evolution the gene family expanded in bivalves generating a large diversity of isoforms with different structures and with a ubiquitous tissue distribution suggesting that chitin is involved in many biological functions. These findings provide insight into CHS evolution in molluscs and lay the foundation for research into their function and response to environmental changes.