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Microbiology ; 159(Pt 1): 176-190, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23154970


Carbon starvation is a common stress for micro-organisms both in nature and in industry. The carbon starvation stress response (CSSR) involves the regulation of several important processes including programmed cell death and reproduction of fungi, secondary metabolite production and extracellular hydrolase formation. To gain insight into the physiological events of CSSR, DNA microarray analyses supplemented with real-time RT-PCR (rRT-PCR) experiments on 99 selected genes were performed. These data demonstrated that carbon starvation induced very complex changes in the transcriptome. Several genes contributing to protein synthesis were upregulated together with genes involved in the unfolded protein stress response. The balance between biosynthesis and degradation moved towards degradation in the case of cell wall, carbohydrate, lipid and nitrogen metabolism, which was accompanied by the production of several hydrolytic enzymes and the induction of macroautophagy. These processes provide the cultures with long-term survival by liberating nutrients through degradation of the cell constituents. The induced synthesis of secondary metabolites, antifungal enzymes and proteins as well as bacterial cell wall-degrading enzymes demonstrated that carbon-starving fungi should have marked effects on the micro-organisms in their surroundings. Due to the increased production of extracellular and vacuolar enzymes during carbon starvation, the importance of the endoplasmic reticulum increased considerably.

Aspergillus nidulans/genética , Aspergillus nidulans/metabolismo , Carbono/metabolismo , Regulação Fúngica da Expressão Gênica , Transcriptoma , Parede Celular/metabolismo , Redes e Vias Metabólicas/genética , Análise em Microsséries , Viabilidade Microbiana , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Estresse Fisiológico
Nat Prod Res ; 22(5): 383-92, 2008 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-18404558


The synthesis of (+/-)-monotesone-A, an antifungal component of Monotes engleri, as well as its four structural analogues were accomplished starting from the corresponding MOM-protected phloracetophenone and benzaldehyde derivatives. Antifungal activities of the five flavanone derivatives were studied against Candida albicans (14053 and ATCC 10231), Candida inconspicua, Candida dubliniensis and Candida krusei.

Antifúngicos/síntese química , Antifúngicos/farmacologia , Flavanonas/síntese química , Flavanonas/farmacologia , Antifúngicos/química , Candida/efeitos dos fármacos , Flavanonas/química , Imunodifusão , Espectroscopia de Ressonância Magnética , Espectroscopia de Infravermelho com Transformada de Fourier , Relação Estrutura-Atividade
Acta Pharm Hung ; 77(1): 5-10, 2007.
Artigo em Húngaro | MEDLINE | ID: mdl-17518107


Flavonoids is one of the most important groups of naturally occurring O-heterocycles possessing a wide range of biological activity. O- and C-prenylated flavanones as members of flavonoids also show remarkable biological activity such as antibacterial, antiviral, anti-tumor, antifungal, anti-HIV and enzyme inhibition activity. O- and C-prenylated flavanones possessing remarkable biological activity are representatives of this family of natural products. In this paper efficient synthetic methods have been reported for the preparation of O-(2, 3) and C-(4, 5) prenylated flavanones isolated from Monotes engleri and their analogues (26-30; 38-43) starting from commercially available starting materials. In vitro pharmacological examinations of our compounds were performed on different Candida species (Candida albicans, Candida inconspicua, Candida dubliniensis, Candida krusei) by agardiffusion method. Our structure-activity relationship study clearly showed that any modification of the structure of selinone (2) and monotesone-A (3) led to the total loss the fungistatic activity.

Antifúngicos/síntese química , Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Flavanonas/síntese química , Flavanonas/farmacologia , Candida albicans/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Modelos Moleculares , Prenilação de Proteína , Relação Estrutura-Atividade
FEMS Yeast Res ; 7(2): 265-75, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17266730


Although exposure of Candida albicans cells to high-dose (4 mM) methylprednisolone stimulated microbial growth, germination rate in serum and phospholipase release, it also promoted the recognition of C. albicans cells by polymorphonuclear leukocytes. Pretreatment of C. albicans cells with methylprednisolone did not result in any increase in the pathogenicity of the fungus in intraperitoneal and intravenous mouse assays. Therefore, the virulence of C. albicans is unlikely to increase in patients treated with comparably high-dose methylprednisolone on skin and mucosal membranes. Methylprednisolone treatments also increased the production of conjugated dienes and thiobarbituric acid-reactive substances, and the menadione sensitivity of C. albicans cells, which can be explained by a significant decrease in the specific activities of several antioxidant enzymes. The combination of methylprednisolone with oxidants, e.g. in topical applications, may be of clinical importance when the predisposition to candidiasis is high. Methylprednisolone treatments negatively affected membrane fluidity and decreased the antifungal effects of both the polyene antibiotic nystatin and the ergosterol biosynthesis inhibitor lovastatin, and also enhanced the deleterious effects of the polyene antimycotic amphotericin B on C. albicans cells. These corticosteroid-polyene drug interactions should be considered in the treatment of C. albicans infections in patients with prolonged topical application of corticosteroids.

Anfotericina B/farmacologia , Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Candida albicans/patogenicidade , Glucocorticoides/administração & dosagem , Metilprednisolona/administração & dosagem , Vitamina K 3/farmacologia , Vitaminas/farmacologia , Animais , Antioxidantes/metabolismo , Candida albicans/crescimento & desenvolvimento , Candida albicans/fisiologia , Candidíase/microbiologia , Permeabilidade da Membrana Celular , Interações de Medicamentos , Feminino , Glucocorticoides/farmacologia , Peroxidação de Lipídeos , Metilprednisolona/farmacologia , Camundongos , Testes de Sensibilidade Microbiana , Estresse Oxidativo , Virulência , Vitamina K 3/administração & dosagem , Vitaminas/administração & dosagem
FEMS Yeast Res ; 6(8): 1140-8, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17156011


Lovastatin inhibited the growth of Candida albicans in a fungistatic way. Although it triggers apoptosis in a great variety of eukaryotic cells, including many tumour cell lines, lovastatin failed to provoke apoptotic events in this human pathogen. The fungistatic behaviour of this statin might arise from its negative influence on membrane fluidity. Because yeast-->pseudomycelium and hyphae morphogenetic transitions took place under exposure to lovastatin morphogenetic switch and apoptotic cell death must be regulated independently in C. albicans.

Antifúngicos/farmacologia , Apoptose/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Lovastatina/farmacologia , Candida albicans/crescimento & desenvolvimento , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Fragmentação do DNA/efeitos dos fármacos , DNA Fúngico/efeitos dos fármacos , Humanos
Fogorv Sz ; 96(2): 61-4, 2003 Apr.
Artigo em Húngaro | MEDLINE | ID: mdl-12762147


The effects of the alkali metals sodium, potassium and lithium on the growth and on certain virulence factors (adhesion, cell-surface hydrophobicity and the germinating ability) of Candida albicans were investigated. It can be concluded that high concentrations of alkali metals possessed an inhibitory effect on the growth of the Candida cells and preincubation in the presence of alkali metals had a negative effect on all the virulence factors studied. It is worth emphasizing that the changes induced during the preincubation persisted even when the high concentrations of the alkali metals were removed from the cell suspension. However, even at high concentrations of sodium or potassium a considerable growth of Candida cells could be measured. Data also showed that although alkali metals could significantly decrease certain virulence traits of the fungus they could not totally inhibit either the adhesion or the germ tube formation potential of the cells. Thus, in spite of the high salt concentrations Candida cells may represent a health hazard in such habitats.

Candida albicans/efeitos dos fármacos , Candida albicans/patogenicidade , Metais Alcalinos/farmacologia , Candida albicans/crescimento & desenvolvimento , Lítio/farmacologia , Potássio/farmacologia , Sódio/farmacologia