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1.
J Fungi (Basel) ; 9(7)2023 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-37504715

RESUMO

The two fungal human pathogens, Candida auris and Candida albicans, possess a variety of virulence mechanisms. Among them are the formation of biofilms to protect yeast against harsh conditions through the development of (pseudo)hyphae whilst also facilitating the invasion of host tissues. In recent years, increased rates of antifungal resistance have been associated with C. albicans and C. auris, posing a significant challenge for the effective treatment of fungal infections. In the course of our ongoing search for novel anti-infectives, six selected azaphilones were tested for their cytotoxicity and antimicrobial effects as well as for their inhibitory activity against biofilm and hyphal formation. This study revealed that rubiginosin C, derived from stromata of the ascomycete Hypoxylon rubiginosum, effectively inhibited the formation of biofilms, pseudohyphae, and hyphae in both C. auris and C. albicans without lethal effects. Crystal violet staining assays were utilized to assess the inhibition of biofilm formation, while complementary microscopic techniques, such as confocal laser scanning microscopy, scanning electron microscopy, and optical microscopy, were used to investigate the underlying mechanisms. Rubiginosin C is one of the few substances known to effectively target both biofilm formation and the yeast-to-hyphae transition of C. albicans and C. auris within a concentration range not affecting host cells, making it a promising candidate for therapeutic intervention in the future.

2.
Nat Commun ; 13(1): 3998, 2022 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-35810180

RESUMO

Basic processes of the fatty acid metabolism have an important impact on the function of intestinal epithelial cells (IEC). However, while the role of cellular fatty acid oxidation is well appreciated, it is not clear how de novo fatty acid synthesis (FAS) influences the biology of IECs. We report here that interfering with de novo FAS by deletion of the enzyme Acetyl-CoA-Carboxylase (ACC)1 in IECs results in the loss of epithelial crypt structures and a specific decline in Lgr5+ intestinal epithelial stem cells (ISC). Mechanistically, ACC1-mediated de novo FAS supports the formation of intestinal organoids and the differentiation of complex crypt structures by sustaining the nuclear accumulation of PPARδ/ß-catenin in ISCs. The dependency of ISCs on cellular de novo FAS is tuned by the availability of environmental lipids, as an excess delivery of external fatty acids is sufficient to rescue the defect in crypt formation. Finally, inhibition of ACC1 reduces the formation of tumors in colitis-associated colon cancer, together highlighting the importance of cellular lipogenesis for sustaining ISC function and providing a potential perspective to colon cancer therapy.


Assuntos
Acetil-CoA Carboxilase , Lipogênese , Acetilcoenzima A/metabolismo , Acetil-CoA Carboxilase/metabolismo , Ácidos Graxos/metabolismo , Lipogênese/fisiologia , Células-Tronco/metabolismo
3.
Eur Arch Psychiatry Clin Neurosci ; 272(6): 929-945, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34595576

RESUMO

This narrative review examines the possible role of microglial cells, first, in neuroinflammation and, second, in schizophrenia, depression, and suicide. Recent research on the interactions between microglia, astrocytes and neurons and their involvement in pathophysiological processes of neuropsychiatric disorders is presented. This review focuses on results from postmortem, positron emission tomography (PET) imaging studies, and animal models of schizophrenia and depression. Third, the effects of antipsychotic and antidepressant drug therapy, and of electroconvulsive therapy on microglial cells are explored and the upcoming development of therapeutic drugs targeting microglia is described. Finally, there is a discussion on the role of microglia in the evolutionary progression of human lineage. This view may contribute to a new understanding of neuropsychiatric disorders.


Assuntos
Transtorno Depressivo Maior , Esquizofrenia , Suicídio , Animais , Humanos , Microglia , Tomografia por Emissão de Pósitrons/métodos , Esquizofrenia/terapia , Suicídio/psicologia
4.
Curr Med Chem ; 28(9): 1841-1873, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32223729

RESUMO

Fungal infections are diseases that are considered neglected although their infection rates have increased worldwide in the last decades. Thus, since the antifungal arsenal is restricted and many strains have shown resistance, new therapeutic alternatives are necessary. Nanoparticles are considered important alternatives to promote drug delivery. In this sense, the objective of the present study was to evaluate the contributions of newly developed nanoparticles to the treatment of fungal infections. Studies have shown that nanoparticles generally improve the biopharmaceutical and pharmacokinetic characteristics of antifungals, which is reflected in a greater pharmacodynamic potential and lower toxicity, as well as the possibility of prolonged action. It also offers the proposition of new routes of administration. Nanotechnology is known to contribute to a new drug delivery system, not only for the control of infectious diseases but for various other diseases as well. In recent years, several studies have emphasized its application in infectious diseases, presenting better alternatives for the treatment of fungal infections.


Assuntos
Micoses , Nanopartículas , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Farmacorresistência Fúngica , Equinocandinas , Humanos , Micoses/tratamento farmacológico
5.
Curr Med Chem ; 28(24): 4935-4953, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33234090

RESUMO

The development of biodegradable nanoparticles is an important tool for the biological transport of chemical compounds. The nanoencapsulation reduces the biopharmaceutical and pharmacokinetic drawbacks of compounds and enhances their biological properties. Naturally occurring polymers such as proteins and polysaccharides have been widely applied in the development of nanostructured systems of several therapeutic agents. Among them is chitosan, a crustacean-carapace-chitin derived biopolymer. In addition to its biocompatibility and biodegradability, chitosan is known for its mucoadhesion properties. Chitosan-based nanostructured systems potentiate most of the aspects of the loaded drugs, including cellular transport and other biological effects. The use of chitosan nanoparticles enhances permeation, stability, and bioactivity of natural compounds. In this review, an overview of the main features of chitosan nanoparticles that improved in vitro and in vivo effects of bioactive natural molecules is given, emphasizing the results obtained with curcumin.


Assuntos
Quitosana , Curcumina , Nanopartículas , Curcumina/farmacologia , Humanos
6.
Antibiotics (Basel) ; 9(11)2020 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-33171584

RESUMO

Infections involving biofilms are difficult to treat due to increased resistances against antibiotics and the immune system. Hence, there is an urgent demand for novel drugs against biofilm infections. During our search for novel biofilm inhibitors from fungi, we isolated linoleic acid from the ascomycete Hypoxylon fragiforme which showed biofilm inhibition of several bacteria at sub-MIC concentrations. Many fatty acids possess antimicrobial activities, but their minimum inhibitory concentrations (MIC) are high and reports on biofilm interferences are scarce. We demonstrated that not only linoleic acid but several unsaturated long-chain fatty acids inhibited biofilms at sub-MIC concentrations. The antibiofilm activity exerted by long-chain fatty acids was mainly against Gram-positive bacteria, especially against Staphylococcus aureus. Micrographs of treated S. aureus biofilms revealed a reduction in the extracellular polymeric substances, pointing to a possible mode of action of fatty acids on S. aureus biofilms. The fatty acids had a strong species specificity. Poly-unsaturated fatty acids had higher activities than saturated ones, but no obvious rule could be found for the optimal length and desaturation for maximal activity. As free fatty acids are non-toxic and ubiquitous in food, they may offer a novel tool, especially in combination with antibiotics, for the control of biofilm infections.

8.
FEMS Microbiol Lett ; 366(14)2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31390020

RESUMO

Actinobacteria are known by their ability to produce several antimicrobial compounds of biotechnological interest. Thus, in this study, we isolated and identified by partial 16S RNA sequencing ∼100 actinobacteria isolates from guarana (Paullinia cupana) bulk soil. Besides, we isolated from the actinobacteria Streptomyces morookaense AM25 a novel cyclic peptide, named gloeosporiocide, molecular formula C44H48N11O7S3 (calculated 938.2901), and characterized by the presence of cyclized cysteins to form three thiazols. The novel compound had activity against the plant pathogen Colletotrichum gloeosporioides, assayed by the paper disk diffusion method (42.7% inhibition, 0.1 mg disk-1) and by the microdilution assay (1.25 g L-1). Our results reveal the potential of the actinobacteria from the Amazon rhizospheric soils as biocontrol agents as well as producers of new compounds with antifungal activity. Thus, this work constitutes a step forward in the development of the biotechnology of actinobacteria in the production of compounds of agronomic interest.


Assuntos
Antibiose , Antifúngicos/isolamento & purificação , Antifúngicos/farmacologia , Peptídeos Cíclicos/isolamento & purificação , Peptídeos Cíclicos/farmacologia , Microbiologia do Solo , Streptomyces/metabolismo , Antifúngicos/química , Cromatografia Líquida de Alta Pressão , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana , Peptídeos Cíclicos/química , Filogenia , RNA Ribossômico 16S/genética , Espectrometria de Massas em Tandem
9.
Infect Immun ; 87(9)2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31285248

RESUMO

Actinobacillus pleuropneumoniae is a capnophilic pathogen of the porcine respiratory tract lacking enzymes of the oxidative branch of the tricarboxylic acid (TCA) cycle. We previously claimed that A. pleuropneumoniae instead uses the reductive branch in order to generate energy and metabolites. Here, we show that bicarbonate and oxaloacetate supported anaerobic growth of A. pleuropneumoniae Isotope mass spectrometry revealed heterotrophic fixation of carbon from stable isotope-labeled bicarbonate by A. pleuropneumoniae, which was confirmed by nano-scale secondary ion mass spectrometry at a single-cell level. By gas chromatography-combustion-isotope ratio mass spectrometry we could further show that the labeled carbon atom is mainly incorporated into the amino acids aspartate and lysine, which are derived from the TCA metabolite oxaloacetate. We therefore suggest that carbon fixation occurs at the interface of glycolysis and the reductive branch of the TCA cycle. The heme precursor δ-aminolevulinic acid supported growth of A. pleuropneumoniae, similar to bicarbonate, implying that anaplerotic carbon fixation is needed for heme synthesis. However, deletion of potential carbon-fixing enzymes, including PEP-carboxylase (PEPC), PEP-carboxykinase (PEPCK), malic enzyme, and oxaloacetate decarboxylase, as well as various combinations thereof, did not affect carbon fixation. Interestingly, generation of a deletion mutant lacking all four enzymes was not possible, suggesting that carbon fixation in A. pleuropneumoniae is an essential metabolic pathway controlled by a redundant set of enzymes. A double deletion mutant lacking PEPC and PEPCK was not impaired in carbon fixation in vitro but showed reduction of virulence in a pig infection model.


Assuntos
Infecções por Actinobacillus/metabolismo , Actinobacillus pleuropneumoniae , Ciclo do Carbono/fisiologia , Pleuropneumonia/metabolismo , Virulência/fisiologia , Actinobacillus pleuropneumoniae/metabolismo , Actinobacillus pleuropneumoniae/patogenicidade , Animais , Modelos Animais de Doenças , Suínos
10.
ISME J ; 13(8): 2018-2030, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30952997

RESUMO

In a given habitat, bacterial cells often experience recurrent exposures to the same environmental stimulus. The ability to memorize the past event and to adjust current behaviors can lead to efficient adaptation to the recurring stimulus. Here we demonstrate that the versatile bacterium Pseudomonas aeruginosa adopts a virulence phenotype after serial passage in the invertebrate model host Galleria mellonella. The virulence phenotype was not linked to the acquisition of genetic variations and was sustained for several generations, despite cultivation of the ex vivo virulence-adapted P. aeruginosa cells under rich medium conditions in vitro. Transcriptional reprogramming seemed to be induced by a host-specific food source, as reprogramming was also observed upon cultivation of P. aeruginosa in rich medium supplemented with polyunsaturated long-chain fatty acids. The establishment of induced memory responses adds a time dimension and seems to fill the gap between long-term evolutionary genotypic adaptation and short-term induced individual responses. Efforts to unravel the fundamental mechanisms that underlie the carry-over effect to induce such memory responses will continue to be of importance as hysteretic behavior can serve survival of bacterial populations in changing and challenging habitats.


Assuntos
Adaptação Fisiológica , Ácidos Graxos Insaturados/metabolismo , Interações Hospedeiro-Patógeno , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/fisiologia , Animais , Mariposas , Fenótipo , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/patogenicidade , Virulência
11.
Acta sci., Biol. sci ; 41: e48785, 20190000. tab, graf
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1460898

RESUMO

Fungi are present in the most diverse environments including the interior of plant tissues, living as endophytes without causing apparent damage. These endophytes are producers of secondary metabolites, also known as natural products, such as fungicides. Here, we evaluated the ethyl acetate fractions obtained from endophytic fungiisolated from plants in the genus Begonia. The fractions were submitted to inhibitorytest against the plant pathogens Diaporthe phaseolorum and Colletotrichum gloeosporioides. From the 88 ethyl acetate fractions evaluated, 14.7 % inhibited C. gloeosporioidesand 11.3 %inhibited D. phaseolorum. One fungal isolate displaying an active fraction was selected for chemical investigation. The fungus identified as Neopestalotiopsissp., produced a compound that was active against D. phaseolorum, with a MIC of 312 μg mL-1(1,695.3 μM). The compound was identified by mass spectrometry and 1H NMR as the known compound fumiquinone B. The results highlight that the endophytes are capable of producing compounds that may be used to control plant pathogens. The compound fumiquinone B is reported for the first time as an antifungal agent against D. phaseolorum, a relevant plant pathogen worldwide. This is also the first report of the production of fumiquinone B by the genus Neopestalotiopsis.


Assuntos
Antifúngicos/metabolismo , Fungos/imunologia
12.
Biomolecules ; 8(4)2018 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-30380779

RESUMO

During the course of our ongoing work to discover new inhibitors of biofilm formation of Staphylococcus aureus from fungal sources, we observed biofilm inhibition by cytochalasans isolated from cultures of the ascomycete Hypoxylon fragiforme for the first time. Two new compounds were purified by a bioassay-guided fractionation procedure; their structures were elucidated subsequently by nuclear magnetic resonance (NMR) spectroscopy and high-resolution mass spectrometry (HR-MS). This unexpected finding prompted us to test further cytochalasans from other fungi and from commercial sources for comparison. Out of 21 cytochalasans, 13 showed significant inhibition of Staphylococcus aureus biofilm formation at subtoxic levels. These findings indicate the potential of cytochalasans as biofilm inhibitors for the first time, also because the minimum inhibitory concentrations (MIC) are independent of the anti-biofilm activities. However, cytochalasans are known to be inhibitors of actin, making some of them very toxic for eukaryotic cells. Since the chemical structures of the tested compounds were rather diverse, the inclusion of additional derivatives, as well as the evaluation of their selectivity against mammalian cells vs. the bacterium, will be necessary as next step in order to develop structure-activity relationships and identify the optimal candidates for development of an anti-biofilm agent.


Assuntos
Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Staphylococcus aureus/fisiologia , Antibacterianos/química , Antibacterianos/isolamento & purificação , Fungos/química , Espectroscopia de Ressonância Magnética , Metaboloma
13.
Front Immunol ; 9: 495, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29675017

RESUMO

Mycobacterium tuberculosis (Mtb), the causative agent of human tuberculosis, is able to efficiently manipulate the host immune system establishing chronic infection, yet the underlying mechanisms of immune evasion are not fully understood. Evidence suggests that this pathogen interferes with host cell lipid metabolism to ensure its persistence. Fatty acid metabolism is regulated by acetyl-CoA carboxylase (ACC) 1 and 2; both isoforms catalyze the conversion of acetyl-CoA into malonyl-CoA, but have distinct roles. ACC1 is located in the cytosol, where it regulates de novo fatty acid synthesis (FAS), while ACC2 is associated with the outer mitochondrial membrane, regulating fatty acid oxidation (FAO). In macrophages, mycobacteria induce metabolic changes that lead to the cytosolic accumulation of lipids. This reprogramming impairs macrophage activation and contributes to chronic infection. In dendritic cells (DCs), FAS has been suggested to underlie optimal cytokine production and antigen presentation, but little is known about the metabolic changes occurring in DCs upon mycobacterial infection and how they affect the outcome of the immune response. We therefore determined the role of fatty acid metabolism in myeloid cells and T cells during Mycobacterium bovis BCG or Mtb infection, using novel genetic mouse models that allow cell-specific deletion of ACC1 and ACC2 in DCs, macrophages, or T cells. Our results demonstrate that de novo FAS is induced in DCs and macrophages upon M. bovis BCG infection. However, ACC1 expression in DCs and macrophages is not required to control mycobacteria. Similarly, absence of ACC2 did not influence the ability of DCs and macrophages to cope with infection. Furthermore, deletion of ACC1 in DCs or macrophages had no effect on systemic pro-inflammatory cytokine production or T cell priming, suggesting that FAS is dispensable for an intact innate response against mycobacteria. In contrast, mice with a deletion of ACC1 specifically in T cells fail to generate efficient T helper 1 responses and succumb early to Mtb infection. In summary, our results reveal ACC1-dependent FAS as a crucial mechanism in T cells, but not DCs or macrophages, to fight against mycobacterial infection.


Assuntos
Células Dendríticas/imunologia , Ácidos Graxos/imunologia , Imunidade Inata , Macrófagos/imunologia , Mycobacterium tuberculosis/imunologia , Células Th1/imunologia , Tuberculose/imunologia , Acetil-CoA Carboxilase/genética , Acetil-CoA Carboxilase/imunologia , Animais , Células Dendríticas/microbiologia , Células Dendríticas/patologia , Ácidos Graxos/genética , Macrófagos/microbiologia , Macrófagos/patologia , Camundongos , Camundongos Knockout , Mycobacterium bovis/imunologia , Mycobacterium tuberculosis/genética , Células Th1/microbiologia , Células Th1/patologia , Tuberculose/genética , Tuberculose/patologia
14.
J Nat Prod ; 81(4): 778-784, 2018 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-29489350

RESUMO

The need for effective compounds to combat antimicrobial resistance and biofilms which play important roles in human infections continues to pose a major health challenge. Seven previously undescribed acyclic diterpenes linked to isocitric acid by an ether linkage, microporenic acids A-G (1-7), were isolated from the cultures of a hitherto undescribed species of the genus Microporus (Polyporales, Basidiomycota) originating from Kenya's Kakamega forest. Microporenic acids D and E (4 and 5) showed antimicrobial activity against a panel of Gram positive bacteria and a yeast, Candida tenuis. Moreover, microporenic acids A and B (1 and 2) demonstrated dose-dependent inhibition of biofilm formation by Staphylococcus aureus. Compound 1 further showed significant activity against Candida albicans and Staphylococcus aureus preformed biofilms.


Assuntos
Anti-Infecciosos/farmacologia , Basidiomycota/química , Biofilmes/efeitos dos fármacos , Animais , Candida albicans/efeitos dos fármacos , Linhagem Celular , Linhagem Celular Tumoral , Bactérias Gram-Positivas/efeitos dos fármacos , Células HeLa , Humanos , Quênia , Camundongos , Testes de Sensibilidade Microbiana/métodos , Staphylococcus aureus/efeitos dos fármacos
15.
Eur Arch Psychiatry Clin Neurosci ; 268(5): 461-470, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28361258

RESUMO

The role of the thalamus in schizophrenia has increasingly been studied in recent years. Deficits in the ventral thalamus have been described in only few postmortem and neuroimaging studies. We utilised our previously introduced neurodevelopmental animal model, the neonatal excitotoxic lesion of the ventral thalamus of Sprague-Dawley rats (Wolf et al., Pharmacopsychiatry 43:99-109, 22). At postnatal day (PD7), male pubs received bilateral thalamic infusions with ibotenic acid (IBA) or artificial cerebrospinal fluid (control). In adulthood, social interaction of two animals not familiar to each other was studied by a computerised video tracking system. This study displays clear lesion effects on social interaction of adult male rats. The significant reduction of total contact time and the significant increase in distance between the animals in the IBA group compared to controls can be interpreted as social withdrawal modelling a negative symptom of schizophrenia. The significant increase of total distance travelled in the IBA group can be hypothesised as agitation modelling a positive symptom of schizophrenia. Using a triple concept of social interaction, the percentage of no social interaction (Non-SI%) was significantly larger, and inversely, the percentage of passive social interaction (SI-passive%) was significantly smaller in the IBA group when compared to controls. In conclusion, on the background of findings in schizophrenic patients, the effects of neonatal ventral thalamic IBA lesions in adult male rats support the hypothesis of face and construct validity as animal model of schizophrenia.


Assuntos
Comportamento Animal/efeitos dos fármacos , Agonistas de Aminoácidos Excitatórios/toxicidade , Ácido Ibotênico/toxicidade , Comportamento Social , Núcleos Ventrais do Tálamo/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Masculino , Atividade Motora/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley
16.
Curr Med Chem ; 25(2): 123-140, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28738771

RESUMO

BACKGROUND: Fumitremorgins are mycotoxins but can also inhibit cancer cells and reverse their drug resistance. OBJECTIVE: The bioactivity of prenylated cyclo-Trp-Pro dipeptides and their derivatives concerning their application in anti-cancer therapies will be discussed. METHODS: Reports on the discovery and assessment of this class of fungal compounds are compiled from literature using Google Scholar and PubMed. The bioactivities of the natural compounds are discussed with the aim of their improvement for cancer therapy. RESULTS: Although a number of compounds of this class have been found, only a minority of them showed bioactivity in the applied bioassays. Fumitremorgins and related compounds are active against various cancer cells but they are also mycotoxins. Some of these natural compounds can arrest cancer cells in their cell cycle and some can block ABC-transporters and reverse resistance in chemotherapy. Structure activity relationships have been deduced leading to the prediction of highly active compounds. Several easily accessible derivatives of these natural products have been discovered being highly selective and non-toxic. CONCLUSION: Sophisticated screening methods, high throughput screening, metabolic engineering, and synthetic biology are novel and promising technologies for the search for highly active drugs. Rapid gene sequencing in combination with engineered biosynthetic pathways should contribute substantially to novel pharmaceutics.


Assuntos
Antineoplásicos/farmacologia , Produtos Biológicos/farmacologia , Indenos/farmacologia , Indóis/farmacologia , Neoplasias/tratamento farmacológico , Antineoplásicos/química , Produtos Biológicos/química , Proliferação de Células/efeitos dos fármacos , Humanos , Indóis/química , Neoplasias/patologia
17.
Microorganisms ; 5(4)2017 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-29231891

RESUMO

Treating infections organized in biofilms is a challenge due to the resistance of the pathogens against antibiotics and host immune cells. Many fungi grow in a wet environment, favorable for the growth of bacterial biofilms, and we speculated that fungi possess some strategies to control these bacterial biofilms. A fungus identified as Hypoxylon fragiforme, was collected in the Harz Mountains, Germany, and its mycelial culture was fermented in different culture media for 67 days to test its biological potential against bacterial biofilms. Sclerin, sclerin diacid and its 3-methyl monoester (methyl 1-(5-hydroxy-6-carboxylic-2,3,4-trimethylphenyl) propionate) are here described for the first time from this fungus. Sclerin and its diacid interfered with the biofilm formation of the pathogen Staphylococcus aureus, inhibiting 86% and 80% of the biofilm at 256 µg mL-1, respectively, but not killing the bacterium. Interestingly, the monomethylester of sclerin diacid was inactive. Although these compounds did not possess any activity against a pre-formed biofilm, they prevented its formation at subtoxic concentrations. Furthermore, sclerin and its diacid displayed a high specificity against Staphylococcus aureus, indicating a good strategy against pathogenic biofilms when combined with antibiotics.

18.
Biol Chem ; 399(1): 13-28, 2017 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-28822220

RESUMO

Eremophilanes are sesquiterpenes with a rearranged carbon skeleton formed both by plants and fungi, however, almost no plant eremophilanes are found in fungi. These eremophilanes possess mainly phytotoxic, antimicrobial, anticancer and immunomodulatory properties and in this review fungal eremophilanes with bioactivities of potential medicinal applications are reviewed and discussed. A special focus is set on natural products bearing highly functionalized fatty acids at C-1 or C-3 position of the eremophilane backbone. Many of these fatty acids seem to contribute to the bioactivity of the metabolites enhancing the activity of the sesquiterpene moieties. Several approaches for optimization of these natural products for clinical needs and testing of the resulting derivatives are presented and discussed. The combination of identification of bioactive natural products with their subsequent improvement using a variety of genetical or chemical tools and the pharmacokinetic assessment of the products is presented here as a promising approach to new drugs.


Assuntos
Anti-Inflamatórios/farmacologia , Inibidores Enzimáticos/farmacologia , Fungos/química , Sesquiterpenos/farmacologia , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/metabolismo , Inibidores Enzimáticos/química , Inibidores Enzimáticos/metabolismo , Fungos/metabolismo , Humanos , Sesquiterpenos/química , Sesquiterpenos/metabolismo
19.
Int J Syst Evol Microbiol ; 67(8): 2804-2810, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28820095

RESUMO

Two Gram-negative, heterotrophic, aerobic, prosthecated, marine bacteria, designated strains MCS23T and MCS27T, were isolated from seawater samples. NaCl was required for growth. The major polar lipid detected in strain MCS27T was phosphatidylglycerol, whereas those detected in MCS23T were phosphatidylglycerol, sulfoquinovosyl diacylglycerol and 1,2-diacyl-3-α-d-glucuronopyranosyl-sn-glycerol taurineamide. The most abundant cellular fatty acids were C18 : 1ω7 and C16 : 0, hydroxyl-fatty acids were 3-OH C12 : 0 in both strains and 3-OH C11 : 0 in MCS23T. Strains MCS23T and MCS27T had DNA G+C contents of 57.0 and 55.0 mol%, respectively. The two strains shared 99.3 % 16S rRNA gene sequence similarity; levels of similarity with the type strains of species of the genus Henriciella were 99.4-97.8 % but DNA-DNA hybridizations were 53 % or lower. Besides their 16S rRNA gene sequences, the novel strains can be differentiated from other species of the genus Henriciella by cell morphology, lipid and fatty acid patterns and enzyme activities. The data obtained led to the identification of two novel species, for which the names Henriciella barbarensis sp. nov. (type strain MCS23T=LMG 28705T=CCUG 66934T) and Henriciella algicola sp. nov. (type strain MCS27T=LMG 29152T=CCUG 67844T) are proposed. As these two novel species are the first prosthecate species in the genus Henriciella, an emended genus description is also provided.


Assuntos
Alphaproteobacteria/classificação , Filogenia , Água do Mar/microbiologia , Alphaproteobacteria/genética , Alphaproteobacteria/isolamento & purificação , Técnicas de Tipagem Bacteriana , Composição de Bases , California , DNA Bacteriano/genética , Ácidos Graxos/análise , Glicolipídeos/química , Hibridização de Ácido Nucleico , Fosfatidilgliceróis/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Ilhas Virgens Americanas
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