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Search results for: ANTIFUNGAL TARGETS · AMINO ACID BIOSYNTHESIS · PROTEIN BIOSYNTHESIS · CANDIDA · ASPERGILLUS · PLANT PATHOGENS
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Molecular targets for antifungals in amino acid and protein biosynthetic pathways
PublicationFungi cause death of over 1.5 million people every year, while cutaneous mycoses are among the most common infections in the world. Mycoses vary greatly in severity, there are long-term skin (ringworm), nail or hair infections (tinea capitis), recurrent like vaginal candidiasis or severe, life-threatening systemic, multiorgan infections. In the last few years, increasing importance is attached to the health and economic problems...
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Inhibitors of amino acids biosynthesis as antifungal agents
PublicationFungal microorganisms, including the human pathogenic yeast and filamentous fungi, are able to synthesize all proteinogenic amino acids, including nine that are essential for humans. A number of enzymes catalyzing particular steps of human-essential amino acid biosynthesis are fungi specific. Numerous studies have shown that auxotrophic mutants of human pathogenic fungi impaired in biosynthesis of particular amino acids exhibit...
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Characterization of two aminotransferases from Candida albicans
PublicationAminoadipate aminotransferase (AmAA) is an enzyme of α-aminoadipate pathway (AAP) for l-lysine biosynthesis. AmAA may also participated in biosynthesis or degradation of aromatic amino acids and in d-tryptophan based pigment production. The AAP is unique for fungal microorganisms. Enzymes involved in this pathway have specific structures and properties. These features can be used as potential molecular markers. Enzymes catalyzing...
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Versatility of putative aromatic aminotransferases from Candida albicans.
PublicationAmino acids constitute the key sources of nitrogen for growth of Candida albicans. In order to survive inside the host in different and rapidly changing environments, this fungus must be able to adapt via its expression of genes for amino acid metabolism. We analysed the ARO8, ARO9, YER152C, and BNA3 genes with regards to their role in the nutritional flexibility of C. albicans. CaAro8p is undoubtedly the most versatile enzyme...
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Enzymes of the lysine biosynthetic pathway as targets for antifungals ?
PublicationSystemic infections caused by human pathogenic fungi in immunocompromized patients continue to be one of the important clinical problems. Limited availability of safe and efficacious antifungal chemotherapeutics and emerging resistance to existing drugs stimulates search for novel molecular targets for antifungals. The α-aminoadipate pathway (AAP) of L-lysine biosynthesis is unique in fungi and thus has been so far considered...
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Phenotypic consequences of the LYS4 gene disruption in Candida albicans
PublicationThe main scientific purpose of our studies was to verify the hypothesis that homoaconitase (HA) from Candida albicans, an enzyme catalyzing a second step of the α-aminoadipate pathway (AAP) of L-Lys biosynthesis may become a new target for antifungal chemotherapy. Previous studies indicated that the A. fumigatus mutant lacking the functional lysF gene, encoding HA, exhibited attenuated virulence in a low-dose mouse infection model...
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Antifungal Effect of Penicillamine Due to the Selective Targeting of L-Homoserine O-Acetyltransferase
PublicationDue to the apparent similarity of fungal and mammalian metabolic pathways, the number of established antifungal targets is low, and the identification of novel ones is highly desirable. The results of our studies, presented in this work, indicate that the fungal biosynthetic pathway of L-methionine, an amino acid essential for humans, seems to be an attractive perspective. The MET2 gene from Candida albicans encoding L-homoserine...
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Novel DNA-binding protein from Nanoarchaeum equitans Kin4-M binds all kinds of nucleic acids
PublicationNanoarchaeum equitans is the only known representative of Archaea phylum Nanoarchaeota and stands out as one of the tiniest known living organism. What is more it has smallest genome, which is only 490.885 base pairs long. It is also one of the most compact genomes. According to predictions about 95% of the DNA encodes proteins or stable RNA. Nanoarchaeum equitans lacks genes for most vital metabolic pathways including lipid, cofactor,...
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Regulated assembly of lipopolysaccharide and sensing of its alterations in Escherichia coli
PublicationThis thesis describes mechanism of the regulation of the transcription of the rpoE gene encoding an essential RNA polymerase subunit in Escherichia coli. The RpoE regulates extracytoplasmic stress response regulon and is required to initiate transcription of genes, whose products are involvedin the folding of periplasmic proteins and synthesis and transport of outer membrane components. The transcriptional regulation of the rpoE...
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Does the chemical modification of Nystatin A1 affect the drug's ability to overcome the multidrug resistance of fungi?
PublicationAlthough the contemporary medicine keeps moving forward, disseminated infections caused by fungal pathogens are an emerging challenge. The dramatic rise of fungal diseases, especially the most life-threatening systemic mycoses is associated with a permanently growing number of immunodeficient patients. Undoubted difficulties in the treatment of fungal infections are caused by lack of highly effective and selective antifungal drugs,...
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Molecular basis of essentiality of early critical steps in the lipopolysaccharide biogenesis in Escherichia coli K-12: requirement of MsbA, cardiolipin, LpxL, LpxM and GcvB
PublicationTo identify the physiological factors that limit the growth of Escherichia coli K-12 strains synthesizing minimal lipopolysaccharide (LPS), we describe the first construction of strains devoid of the entire waa locus and concomitantly lacking all three acyltransferases (LpxL/LpxM/LpxP), synthesizing minimal lipid IVA derivatives with a restricted ability to grow at around 21 °C. Suppressors restoring growth up to 37 °C of Δ(gmhD-waaA)...
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Elicitation strategies for the improvement of essential oil content in Rhododendron tomentosum (Ledum palustre) bioreactor-grown microshoots
PublicationRhododendron tomentosum Harmaja, previously Ledum palustre L., is a fragrant plant growing in swampy areas, which is characterized by well-known repellent properties and the anti-arthritic potential. In the present study, R. tomentosum microshoots cultivated in RITA® bioreactor, providing the alternative, environment-independent source of the valuable essential oil, were treated for 7 days with copper and nickel salts, methyl jasmonate,...
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A new factor LapD is required for the regulation of LpxC amounts and lipopolysaccharide trafficking
PublicationLipopolysaccharide (LPS) constitutes the major component of the outer membrane and is essential for bacteria, such as Escherichia coli. Recent work has revealed the essential roles of LapB and LapC proteins in regulating LPS amounts; although, if any additional partners are involved is unknown. Examination of proteins co-purifying with LapB identified LapD as a new partner. The purification of LapD reveals that it forms a complex...
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Heptaene macrolides biosynthesis by Streptomyces species
PublicationPolyene macrolides are one of the groups of secondary metabolites, generated by microorganisms belonging to the Streptomyces genus. These compounds, containing 3 - 7 conjugated double bonds systems in their molecules exhibit high antifungal activity against a broad spectrum of fungal pathogens with heptaenes demonstrating the highest antifungal potential. At the large extent, efficiency of biosynthesis of these natural products...
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Lipopolysaccharides: regulated biosynthesis and structural diversity
PublicationThe cell envelope of Gram-negative bacteria contains two distinct membranes, an inner (IM) and an outer (OM) membrane, separated by the periplasm, a hydrophilic compartment that includes a thin layer of peptidoglycan. The most distinguishing feature of such bacteria is the presence of an asymmetric OM with phospholipids located in the inner leaflet and lipopolysaccharides (LPSs) facing the outer leaflet. The maintenance of this...
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Synthesis of 2-amino-2,6-dideoxy-D-glucitol-6-sulfonic acid as a potential antifungal agent.
PublicationGlucosamine-6P (GlcN-6P) synthase catalyzes the first committed step in the biosynthetic pathway leading to the formation of UDP-GlcNAc, a sugar nucleotide precursor providing D-glucosamine for the formation of chitin and manoproteins. 2-Amino-2,6-dideoxy-D-glucitol-6-sulfonic acid is an analog of 2-amino-2-deoxy-D-glucitol 6-phosphate (GlcN-ol-6-P), a known inhibitor of GlcN-6-P synthase, in which the phosphate group of the latter...
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Suppressors of lapC mutation identify new regulators of LpxC, which mediates the first committed step in lipopolysaccharide biosynthesis
PublicationGram-negative bacteria, such as Escherichia coli, are characterized by an asymmetric outer membrane (OM) with lipopolysaccharide (LPS) located in the outer leaflet and phospholipids facing the inner leaflet. E. coli recruits LPS assembly proteins LapB, LapC and LapD in concert with FtsH protease to ensure a balanced biosynthesis of LPS and phospholipids. We recently reported that bacteria either lacking the periplasmic domain of...
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Amino Acid Based Antimicrobial Agents – Synthesis and Properties
PublicationStructures of several dozen of known antibacterial, antifungal or antiprotozoal agents are based on the amino acid scaffold. In most of them, the amino acid skeleton is of a crucial importance for their antimicrobial activity, since very often they are structural analogs of amino acid intermediates of different microbial biosynthetic pathways. Particularly, some aminophosphonate or aminoboronate analogs of protein amino acids are...
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Molecular Targets for Anticandidal Chemotherapy
PublicationA relatively small number of anticandidal chemotherapeutics used in clinical practice is at least in part consequence of a limited number of their molecular targets: ergosterol in the membrane, lanosterol demethylase, b(1!3) glucan synthase, and DNA/RNA biosynthesis. Much more potential novel targets have been revealed by the comparative genomic studies identifying essential genes unique for Candida albicans or resulted from recognition...
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Enzymes of UDP-GlcNAc biosynthesis in yeast
PublicationD-glukozamina stanowi ważny składnik budulcowy głównych elementów strukturalnych grzybowej ściany komórkowej: chityny, chitozanu i mannoprotein. Inne aminocukry, takie jak D-mannozamina i D-galaktozamina, stosunkowo powszechne w komórkach wyższych organizmów eukariotycznych, rzadko występują u grzybów i są praktycznie nieobecne w komórkach drożdży i drożdżaków. Zawierający glukozaminę nukleotyd cukrowy UDP-GlcNAc jest syntezowany...