RESUMO
The Streptomyces genus comprises Gram-positive bacteria known to produce over two-thirds of the antibiotics used in medical practice. The biosynthesis of these secondary metabolites is highly regulated and influenced by a range of nutrients present in the growth medium. In Streptomyces coelicolor, glucose inhibits the production of actinorhodin (ACT) and undecylprodigiosin (RED) by a process known as carbon catabolite repression (CCR). However, the mechanism mediated by this carbon source still needs to be understood. It has been observed that glucose alters the transcriptomic profile of this actinobacteria, modifying different transcriptional regulators, including some of the one- and two-component systems (TCSs). Under glucose repression, the expression of one of these TCSs SCO6162/SCO6163 was negatively affected. We aimed to study the role of this TCS on secondary metabolite formation to define its influence in this general regulatory process and likely establish its relationship with other transcriptional regulators affecting antibiotic biosynthesis in the Streptomyces genus. In this work, in silico predictions suggested that this TCS can regulate the production of the secondary metabolites ACT and RED by transcriptional regulation and protein-protein interactions of the transcriptional factors (TFs) with other TCSs. These predictions were supported by experimental procedures such as deletion and complementation of the TFs and qPCR experiments. Our results suggest that in the presence of glucose, the TCS SCO6162/SCO6163, named GarR/GarS, is an important negative regulator of the ACT and RED production in S. coelicolor. KEY POINTS: ⢠GarR/GarS is a TCS with domains for signal transduction and response regulation ⢠GarR/GarS is an essential negative regulator of the ACT and RED production ⢠GarR/GarS putatively interacts with and regulates activators of ACT and RED.
Assuntos
Proteínas de Bactérias , Regulação Bacteriana da Expressão Gênica , Streptomyces coelicolor , Antraquinonas/metabolismo , Antibacterianos/biossíntese , Antibacterianos/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Benzoisocromanequinonas , Repressão Catabólica , Glucose/metabolismo , Prodigiosina/análogos & derivados , Prodigiosina/biossíntese , Prodigiosina/metabolismo , Metabolismo Secundário/genética , Streptomyces coelicolor/metabolismo , Streptomyces coelicolor/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
Bionanocomposites based on natural bioactive entities have gained importance due to their abundance; renewable and environmentally benign nature; and outstanding properties with applied perspective. Additionally, their formulation with biological molecules with antimicrobial, antioxidant, and anticancer activities has been produced nowadays. The present review details the state of the art and the importance of this pyrrolic compound produced by microorganisms, with interest towards Serratia marcescens, including production strategies at a laboratory level and scale-up to bioreactors. Promising results of its biological activity have been reported to date, and the advances and applications in bionanocomposites are the most recent strategy to potentiate and to obtain new carriers for the transport and controlled release of prodigiosin. Prodigiosin, a bioactive secondary metabolite, produced by Serratia marcescens, is an effective proapoptotic agent against bacterial and fungal strains as well as cancer cell lines. Furthermore, this molecule presents antioxidant activity, which makes it ideal for treating wounds and promoting the general improvement of the immune system. Likewise, some of the characteristics of prodigiosin, such as hydrophobicity, limit its use for medical and biotechnological applications; however, this can be overcome by using it as a component of a bionanocomposite. This review focuses on the chemistry and the structure of the bionanocomposites currently developed using biorenewable resources. Moreover, the work illuminates recent developments in pyrrole-based bionanocomposites, with special insight to its application in the medical area.
Assuntos
Nanocompostos , Prodigiosina , Antibacterianos/química , Reatores Biológicos , Prodigiosina/química , Prodigiosina/farmacologia , Serratia marcescens/químicaRESUMO
Pigments are among the most fascinating molecules found in nature and used by human civilizations since the prehistoric ages. Although most of the bio-dyes reported in the literature were discovered around the eighties, the necessity to explore novel compounds for new biological applications has made them resurface as potential alternatives. Prodigiosin (PG) is an alkaloid red bio-dye produced by diverse microorganisms and composed of a linear tripyrrole chemical structure. PG emerges as a really interesting tool since it shows a wide spectrum of biological activities, such as antibacterial, antifungal, algicidal, anti-Chagas, anti-amoebic, antimalarial, anticancer, antiparasitic, antiviral, and/or immunosuppressive. However, PG vehiculation into different delivery systems has been proposed since possesses low bioavailability because of its high hydrophobic character (XLogP3-AA = 4.5). In the present review, the general aspects of the PG correlated with synthesis, production process, and biological activities are reported. Besides, some of the most relevant PG delivery systems described in the literature, as well as novel unexplored applications to potentiate its biological activity in biomedical applications, are proposed.
Assuntos
Antineoplásicos , Prodigiosina , Antibacterianos/farmacologia , Antifúngicos , Humanos , Prodigiosina/farmacologia , Serratia marcescens/químicaRESUMO
Serratia marcescens is a bacterial species that produces an antibacterial pigment (Prodigiosin) showing a wide adaptive response to environmental stresses. The study aimed to investigate Prodigiosin production in S. marcescens wild-type strains, as well as its relation to photoprotection and antigenotoxicity against UVB. Prodigiosin yield was spectrophotometrically assayed in extracts of bacterial strains grown in different culture media. In vitro photoprotection efficacy was evaluated using the in vitro indices sun protection factor (SPFin vitro ) and critical wavelength (λc). The percentage of UVB antigenotoxicity estimates (%GI) in the SOS Chromotest was also evaluated. Correlation analysis was used to examine the relationship between Prodigiosin yield, SPFin vitro , %GI estimates and environmental traits (altitude, temperature, rainfall and solar irradiance). Prodigiosin yield in S. marcescens strains varied depending on culture media used for its growth, and it was correlated with environmental variables such as temperature and solar irradiance. SPFin vitro estimates were well correlated with Prodigiosin concentration and %GI values in the bacterial strains being studied. UVB photoprotective efficacy of the extracts obtained from S. marcescens strains depends on the strain's Prodigiosin yield and its antigenotoxic potential. The extracts with Prodigiosin yield higher than ~17 µg mL-1 could be used as sources of sunscreen ingredients.
Assuntos
Prodigiosina , Serratia marcescens , Colômbia , Meios de Cultura , Extratos Vegetais , Prodigiosina/farmacologia , Serratia marcescens/fisiologiaRESUMO
This work aimed to investigate the production of prodigiosin by S. marcescens UCP 1549 in solid-state fermentation (SSF), as a sustainable alternative for reducing the production costs and environmental impact. Thus, different agro-industrial substrates were used in the formulation of the prodigiosin production medium, obtaining the maximum yield of pigment (119.8 g/kg dry substrate) in medium consisting of 5 g wheat bran, 5% waste soybean oil and saline solution. The pigment was confirmed as prodigiosin by the maximum absorbance peak at 535 nm, Rf 0.9 in TLC, and the functional groups by infrared spectrum (FTIR). Prodigiosin demonstrated stability at different values of temperature, pH and NaCl concentrations and antimicrobial properties, as well as not show any toxicity. These results confirm the applicability of SSF as a sustainable and promising technology and wheat bran as potential agrosubstrate to produce prodigiosin, making the bioprocess economic and competitive for industrial purposes.
Assuntos
Microbiologia Industrial , Prodigiosina , Serratia marcescens , Antibacterianos/biossíntese , Meios de Cultura/química , Fermentação , Microbiologia Industrial/métodos , Prodigiosina/biossíntese , Serratia marcescens/metabolismoRESUMO
Atherosclerosis is a chronic inflammatory disease, whose progression and stability are modulated, among other factors, by an innate and adaptive immune response. Prodiginines are bacterial secondary metabolites with antiproliferative and immunomodulatory activities; however, their effect on the progression or vulnerability of atheromatous plaque has not been evaluated. This study assessed the therapeutic potential of prodigiosin and undecylprodigiosin on inflammatory marker expression and atherosclerosis. An in vitro and in vivo study was carried out. Migration, low-density lipoprotein (LDL) uptake and angiogenesis assays were performed on cell types involved in the pathophysiology of atherosclerosis. In addition, male LDL receptor null (Ldlr-/-) C57BL/6J mice were treated with prodigiosin or undecylprodigiosin for 28 days. Morphometric analysis of atherosclerotic plaques, gene expression of atherogenic factors in the aortic sinus and serum cytokine quantification were performed. The treatments applied had slight effects on the in vitro tests performed, highlighting the inhibitory effect on the migration of SMCs (smooth muscle cells). On the other hand, although no significant difference in atherosclerotic plaque progression was observed, gene expression of IL-4 and chemokine (C-C motif) ligand 2 (Ccl2) was downregulated. In addition, 50 µg/Kg/day of both treatments was sufficient to inhibit circulating tumor necrosis factor alpha (TNF-α), interleukin-2 (IL-2) and interferon-gamma (IFN-γ) in serum. These results suggested that prodigiosin and undecylprodigiosin modulated inflammatory markers and could have an impact in reducing atherosclerotic plaque vulnerability.
Assuntos
Aterosclerose/imunologia , Regulação da Expressão Gênica/efeitos dos fármacos , Imunidade/efeitos dos fármacos , Prodigiosina/análogos & derivados , Receptores de LDL/fisiologia , Animais , Aterosclerose/tratamento farmacológico , Aterosclerose/patologia , Citocinas/metabolismo , Imunossupressores/farmacologia , Lipídeos/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Prodigiosina/farmacologiaRESUMO
Melanoma is a type of skin cancer with an elevated incidence of metastasis and chemoresistance. Such features hamper treatment success of these neoplasms, demanding the search for new therapeutic options. Using a two-step resin-based approach, we recently demonstrated that cytotoxic prodiginines bind to the inhibitor of apoptosis protein, survivin. Herein, we explore the role of survivin in melanoma and whether its modulation is related to the antimelanoma properties of three cytotoxic prodiginines (prodigiosin, cyclononylprodigiosin, and nonylprodigiosin) isolated from marine bacteria. In melanoma patients and cell lines, survivin is overexpressed, and higher levels negatively impact survival. All three prodiginines caused a decrease in cell growth with reduced cytotoxicity after 24 h compared to 72 h treatment, suggesting that low concentrations promote cytostatic effects in SK-Mel-19 (BRAF mutant) and SK-Mel-28 (BRAF mutant), but not in SK-Mel-147 (NRAS mutant). An increase in G1 population was observed after 24 h treatment with prodigiosin and cyclononylprodigiosin in SK-Mel-19. Further studies indicate that prodigiosin induced apoptosis and DNA damage, as detected by increased caspase-3 cleavage and histone H2AX phosphorylation, further arguing for the downregulation of survivin. Computer simulations suggest that prodigiosin and cyclononylprodigiosin bind to the BIR domain of survivin. Moreover, knockdown of survivin increased long-term toxicity of prodigiosin, as observed by reduced clonogenic capacity, but did not alter short-term cytotoxicity. In summary, prodiginine treatment provoked cytostatic rather than cytotoxic effects, cell cycle arrest at G0/G1 phase, induction of apoptosis and DNA damage, downregulation of survivin, and decreased clonogenic capacity in survivin knockdown cells.
Assuntos
Melanoma/metabolismo , Prodigiosina/análogos & derivados , Prodigiosina/farmacologia , Survivina/antagonistas & inibidores , Survivina/biossíntese , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Dano ao DNA/efeitos dos fármacos , Dano ao DNA/fisiologia , Relação Dose-Resposta a Droga , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/fisiologia , Humanos , Melanoma/tratamento farmacológico , Prodigiosina/uso terapêutico , Survivina/genéticaRESUMO
A novel pigmented bacterium, initially identified as 11E, was isolated from a site historically known to have various iron-related ores. Phylogenetic analysis of this bacterial strain showed that it belongs to Serratia marcescens. This pigmented S. marcescens 11E cultured individually with glucose, acetate, and glycerol as electron donors along with the soluble electron acceptor iron (Fe) (III) citrate offered a large reduction extent (45.3 %, 31.4 %, and 13.5 %, respectively). On the other hand, when iron oxide (Fe2O3) is used as electron acceptor, the pigmented strain produced a null reduction extent. Surprisingly, the absence of prodigiosin on the bacterial surface (non-pigmented strain) resulted in a large reduction extent of the non-soluble iron form (20-49%). All these extents were comparable and, in some cases, superior to those presented in the literature. Additionally, in the present study, it was found that anthraquinone sulfonate (AQS) stimulated Fe(III) reduction of soluble and non-soluble Fe species only with pigmented S. marcescens. In contrast, in the culture media with the non-pigmented strain, the presence of AQS did not stimulate the Fe(III) reduction. These results suggest that the pigmented phenotype of S. marcescens 11E may perform non-soluble Fe(III) reduction by electron shuttling. In contrast, for the non-pigmented phenotype of this bacterium, non-soluble Fe(III) reduction seems to proceed by direct contact. Our study demonstrates that this bacterium may be used in bioreduction process of heavy metals or as a biocatalyst in bioelectrochemical devices.
Assuntos
Compostos Férricos/metabolismo , Prodigiosina/metabolismo , Serratia marcescens , Enzimas , Filogenia , RNA Ribossômico 16S/genética , Serratia marcescens/genética , Serratia marcescens/isolamento & purificação , Serratia marcescens/metabolismoRESUMO
Background: Prodigiosin has been demonstrated to be an important candidate in investigating anticancer drugs and in many other applications in recent years. However, industrial production of prodigiosin has not been achieved. In this study, we found a prodigiosin-producing strain, Serratia marcescens FZSF02, and its fermentation strategies were studied to achieve the maximum yield of prodigiosin. Results: When the culture medium consisted of 16.97 g/L of peanut powder, 16.02 g/L of beef extract, and 11.29 mL/L of olive oil, prodigiosin reached a yield of 13.622 ± 236 mg/L after culturing at 26 °C for 72 h. Furthermore, when 10 mL/L olive oil was added to the fermentation broth at the 24th hour of fermentation, the maximum prodigiosin production of 15,420.9 mg/L was obtained, which was 9.3-fold higher than the initial level before medium optimization. More than 60% of the prodigiosin produced with this optimized fermentation strategy was in the form of pigment pellets. To the best of our knowledge, this is the first report on this phenomenon of pigment pellet formation, which made it much easier to extract prodigiosin at low cost. Prodigiosin was then purified and identified by absorption spectroscopy, HPLC, and LCMS. Purified prodigiosin obtained in this study showed anticancer activity in separate experiments on several human cell cultures: A549, K562, HL60, HepG2, and HCT116. Conclusions: This is a promising strain for producing prodigiosin. The prodigiosin has potential in anticancer medicine studies.
Assuntos
Prodigiosina/biossíntese , Prodigiosina/farmacologia , Serratia marcescens/metabolismo , Antineoplásicos/farmacologia , Arachis/química , Pós , Prodigiosina/isolamento & purificação , Espectrometria de Massas , Células Tumorais Cultivadas/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Técnicas de Cultura de Células , Fermentação , Azeite de Oliva/química , Acetatos , NitrogênioRESUMO
Se denomina hemoptisis a la expulsión de sangre procedente del árbol traqueobronquial, es por ello que siempre habrá que descartar sangrado de cavidad oral, nasofaringe y tracto digestivo. De esta forma, la expectoración de sangre de una fuente que no es el tracto respiratorio inferior se denomina pseudohemoptisis, siendo sus causas la hematemesis, los tumores nasofaríngeos y digestivos, la sobredosis de rifampicina y la neumonía por Serratia marcescens. Esta bacteria patógena es la única descripta en la bibliografía como causa de pseudohemoptisis por ser productora de un pigmento rojizo denominado prodigiosina. En su diagnóstico, además de los cultivos de muestras respiratorias y hemocultivos, juega un rol importante la búsqueda de hematíes en esputo, los cuales se encuentran ausentes cuando el pigmento es el responsable de la coloración de la muestra
Assuntos
Prodigiosina , Serratia , HemoptiseRESUMO
This work aimed to explore the action of natural prodigiosin on both bacterial organisms and Trypanosoma cruzi cells. Methods: Natural prodigiosin pigment was extracted and purified from cultures of Serratia marcescens. Two media, peanut broth and peptone glycerol broth, both recommended in the literature for prodigiosin production, were compared. The prodigiosin obtained was employed to explore its antimicrobial properties against both bacteria and Trypanosoma cruzi cells. Results: Peanut broth yielded four times more prodigiosin. The prodigiosin showed remarkable activity (minimal inhibitory concentrations in the range of 2-8 µM for bacteria and half maximal inhibitory concentration of 0.6 µM for Trypanosoma cruzi). In fact, the prodigiosin concentration required to inhibit parasite growth was as low as 0.25 mg/l versus 4.9 mg/l of benznidazole required. Furthermore, atomic force microscopy revealed marked morphological alterations in treated epimastigote forms, although no pore-formation activity was detected in protein-free environments. Conclusions: This work demonstrates the potential usefulness of prodigiosin against some gram-positive and gram-negative bacteria and Trypanosoma cruzi although further studies must be done in order to assess its value as a candidate molecule.(AU)
Assuntos
Animais , Prodigiosina/uso terapêutico , Trypanosoma cruzi , Doença de Chagas , Bactérias Gram-NegativasRESUMO
Weaning results in intestinal dysfunction, mucosal atrophy, transient anorexia, and intestinal barrier defects. In this study, the effect of prodigiosin (PG) on the intestinal inflammation of weaned rats was investigated by using 1H-NMR spectroscopy and biochemistry indexes to regulate the intestinal metabolism. After administration for 14 days, the body mass of the PG group was increased by 1.29- and 1.26-fold compared with those of the control and alcohol groups, respectively, using a dose of 200 µg PG·kg-1 body weight per day. PG increased organic acid content and decreased moisture, pH values, and free ammonia in feces. In addition, PG alleviated the intestinal inflammation of weaned rats. The analysis of 1H-NMR signal peak attribution and the model validation of metabolic data of feces contents showed that PG significantly affected the metabolism of small molecular compounds in the intestinal tract of weaned rats. This study presents the promising alternative of using PG to alleviate intestinal inflammation effectively in the intestinal tract of weaned rats.
Assuntos
Animais , Masculino , Ratos , Prodigiosina/efeitos adversos , Desmame , Bioquímica/classificação , Espectroscopia de Prótons por Ressonância Magnética/métodos , Inflamação/classificação , Anorexia , Dosagem/efeitos adversos , Concentração de Íons de Hidrogênio , Metabolismo/efeitos dos fármacosRESUMO
BACKGROUND: In Streptomyces, understanding the switch from primary to secondary metabolism is important for maximizing the production of secondary metabolites such as antibiotics, as well as for optimizing recombinant glycoprotein production. Differences in Streptomyces lividans bacterial aggregation as well as recombinant glycoprotein production and O-mannosylation have been reported due to modifications in the shake flask design. We hypothetized that such differences are related to the metabolic switch that occurs under oxygen-limiting conditions in the cultures. RESULTS: Shake flask design was found to affect undecylprodigiosin (RED, a marker of secondary metabolism) production; the RED yield was 12 and 385 times greater in conventional normal Erlenmeyer flasks (NF) than in baffled flasks (BF) and coiled flasks (CF), respectively. In addition, oxygen transfer rates (OTR) and carbon dioxide transfer rates were almost 15 times greater in cultures in CF and BF as compared with those in NF. Based on these data, we obtained respiration quotients (RQ) consistent with aerobic metabolism for CF and BF, but an RQ suggestive of anaerobic metabolism for NF. CONCLUSION: Although the metabolic switch is usually related to limitations in phosphate and nitrogen in Streptomyces sp., our results reveal that it can also be activated by low OTR, dramatically affecting recombinant glycoprotein production and O-mannosylation and increasing RED synthesis in the process.
Assuntos
Reatores Biológicos/microbiologia , Oxigênio/farmacologia , Recombinação Genética/genética , Streptomyces lividans/metabolismo , Cinética , Redes e Vias Metabólicas/efeitos dos fármacos , Prodigiosina/análogos & derivados , Prodigiosina/biossíntese , Prodigiosina/química , Espectroscopia de Infravermelho com Transformada de Fourier , Streptomyces lividans/efeitos dos fármacos , Streptomyces lividans/crescimento & desenvolvimentoRESUMO
Symbiotic bacteria can produce secondary metabolites and volatile compounds that contribute to amphibian skin defense. Some of these symbionts have been used as probiotics to treat or prevent the emerging disease chytridiomycosis. We examined 20 amphibian cutaneous bacteria for the production of prodigiosin or violacein, brightly colored defense compounds that pigment the bacteria and have characteristic spectroscopic properties making them readily detectable, and evaluated the antifungal activity of these compounds. We detected violacein from all six isolates of Janthinobacterium lividum on frogs from the USA, Switzerland, and on captive frogs originally from Panama. We detected prodigiosin from five isolates of Serratia plymuthica or S. marcescens, but not from four isolates of S. fonticola or S. liquefaciens. All J. lividum isolates produced violacein when visibly purple, while prodigiosin was only detected on visibly red Serratia isolates. When applied to cultures of chytrid fungi Batrachochytrium dendrobatidis (Bd) and B. salamandrivorans (Bsal), prodigiosin caused significant growth inhibition, with minimal inhibitory concentrations (MIC) of 10 and 50 µM, respectively. Violacein showed a MIC of 15 µM against both fungi and was slightly more active against Bsal than Bd at lower concentrations. Although neither violacein nor prodigiosin showed aerosol activity and is not considered a volatile organic compound (VOC), J. lividum and several Serratia isolates did produce antifungal VOCs. White Serratia isolates with undetectable prodigiosin levels could still inhibit Bd growth indicating additional antifungal compounds in their chemical arsenals. Similarly, J. lividum can produce antifungal compounds such as indole-3-carboxaldehyde in addition to violacein, and isolates are not always purple, or turn purple under certain growth conditions. When Serratia isolates were grown in the presence of cell-free supernatant (CFS) from the fungi, CFS from Bd inhibited growth of the prodigiosin-producing isolates, perhaps indicative of an evolutionary arms race; Bsal CFS did not inhibit bacterial growth. In contrast, growth of one J. lividum isolate was facilitated by CFS from both fungi. Isolates that grow and continue to produce antifungal compounds in the presence of pathogens may represent promising probiotics for amphibians infected or at risk of chytridiomycosis. In a global analysis, 89% of tested Serratia isolates and 82% of J. lividum isolates were capable of inhibiting Bd and these have been reported from anurans and caudates from five continents, indicating their widespread distribution and potential for host benefit.
Assuntos
Bactérias/metabolismo , Quitridiomicetos/efeitos dos fármacos , Indóis/antagonistas & inibidores , Indóis/metabolismo , Prodigiosina/antagonistas & inibidores , Prodigiosina/metabolismo , Compostos Orgânicos Voláteis/antagonistas & inibidores , Compostos Orgânicos Voláteis/metabolismo , Animais , Antifúngicos/farmacologia , Anuros/microbiologia , Bactérias/classificação , Bactérias/isolamento & purificação , Agentes de Controle Biológico/antagonistas & inibidores , Quitridiomicetos/crescimento & desenvolvimento , Quitridiomicetos/patogenicidade , Indóis/química , Testes de Sensibilidade Microbiana , Panamá , Filogenia , Prodigiosina/química , Serratia/classificação , Serratia/isolamento & purificação , Serratia/metabolismo , Pele/microbiologia , Suíça , Simbiose , Estados Unidos , Compostos Orgânicos Voláteis/químicaRESUMO
In the genus Streptomyces, carbon utilization is of significant importance for the expression of genes involved in morphological differentiation and antibiotic production. However, there is little information about the mechanism involved in these effects. In the present work, it was found that glucose exerted a suppressive effect on the Streptomyces coelicolor actinorhodin (Act) and undecylprodigiosin (Red) production, as well as in its morphological differentiation. Accordingly, using a high-density microarray approach in S. coelicolor grown under glucose repression, at early growth stages, a negative effect was exerted on the transcription of genes involved in Act and Red production, when compared with non-repressive conditions. Seven genes of Act and at least ten genes of Red production were down-regulated by glucose. Stronger repression was observed on the initial steps of antibiotics formation. On the contrary, the coelimycin P1 cluster was up-regulated by glucose. Regarding differentiation, no sporulation was observed in the presence of glucose and expression of a set of genes of the bld cascade was repressed as well as chaplins and rodlins genes. Finally, a series of transcriptional regulators involved in both processes were up- or down-regulated by glucose. This is the first global transcriptomic approach performed to understand the molecular basis of the glucose effect on the synthesis of secondary metabolism and differentiation in the genus Streptomyces. The results of this study are opening new avenues for further exploration.
Assuntos
Carbono/metabolismo , Metabolismo Secundário , Streptomyces coelicolor/citologia , Streptomyces coelicolor/metabolismo , Antraquinonas/metabolismo , Antibacterianos/farmacologia , Perfilação da Expressão Gênica , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Genes Bacterianos , Glucose/farmacologia , Prodigiosina/análogos & derivados , Prodigiosina/biossíntese , Reação em Cadeia da Polimerase em Tempo Real , Reprodutibilidade dos Testes , Metabolismo Secundário/efeitos dos fármacos , Metabolismo Secundário/genética , Streptomyces coelicolor/efeitos dos fármacos , Streptomyces coelicolor/genéticaRESUMO
This work addresses the production of prodigiosin from ram horn peptone (RHP) using MO-1, a local isolate in submerged culture. First, a novel gram-negative and rod-shaped bacterial strain, MO-1, was isolated from the body of the grasshopper (Poecilemon tauricola Ramme 1951), which was collected from pesticide-contaminated fields. Sequence analysis of 16S rDNA classified the microbe as Serratia marcescens. The substrate utilization potential (BIOLOG) and fatty acid methyl ester profile (FAME) of S. marcescens were also determined. The effect of RHP on the production of prodigiosin by S. marcescens MO-1 was investigated, and the results showed that RHP supplementation promoted the growth of MO-1 and increased the production of prodigiosin. A concentration of 0.4% (w/v) RHP resulted in the greatest yield of prodigiosin (277.74 mg/L) after 48 h when mannitol was used as the sole source of carbon. The pigment yield was also influenced by the types of carbon sources and peptones. As a result, RHP was demonstrated to be a suitable substrate for prodigiosin production. These results revealed that prodigiosin could be produced efficiently by S. marcescens using RHP.
Assuntos
Meios de Cultura/química , Peptonas/metabolismo , Prodigiosina/metabolismo , Serratia marcescens/crescimento & desenvolvimento , Serratia marcescens/metabolismo , Animais , Técnicas de Tipagem Bacteriana , Análise por Conglomerados , Citosol/química , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Ribossômico/química , DNA Ribossômico/genética , Ácidos Graxos/análise , Gafanhotos/microbiologia , Dados de Sequência Molecular , Filogenia , Pigmentos Biológicos/metabolismo , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Serratia marcescens/classificação , Serratia marcescens/isolamento & purificaçãoRESUMO
This work addresses the production of prodigiosin from ram horn peptone (RHP) using MO-1, a local isolate in submerged culture. First, a novel gram-negative and rod-shaped bacterial strain, MO-1, was isolated from the body of the grasshopper (Poecilemon tauricola Ramme 1951), which was collected from pesticide-contaminated fields. Sequence analysis of 16S rDNA classified the microbe as Serratia marcescens. The substrate utilization potential (BIOLOG) and fatty acid methyl ester profile (FAME) of S. marcescens were also determined. The effect of RHP on the production of prodigiosin by S. marcescens MO-1 was investigated, and the results showed that RHP supplementation promoted the growth of MO-1 and increased the production of prodigiosin. A concentration of 0.4% (w/v) RHP resulted in the greatest yield of prodigiosin (277.74 mg/L) after 48 h when mannitol was used as the sole source of carbon. The pigment yield was also influenced by the types of carbon sources and peptones. As a result, RHP was demonstrated to be a suitable substrate for prodigiosin production. These results revealed that prodigiosin could be produced efficiently by S. marcescens using RHP.
Assuntos
Animais , Meios de Cultura/química , Peptonas/metabolismo , Prodigiosina/metabolismo , Serratia marcescens/crescimento & desenvolvimento , Serratia marcescens/metabolismo , Técnicas de Tipagem Bacteriana , Análise por Conglomerados , Citosol/química , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Ribossômico/química , DNA Ribossômico/genética , Ácidos Graxos/análise , Gafanhotos/microbiologia , Dados de Sequência Molecular , Filogenia , Pigmentos Biológicos/metabolismo , /genética , Análise de Sequência de DNA , Serratia marcescens/classificação , Serratia marcescens/isolamento & purificaçãoRESUMO
This work addresses the production of prodigiosin from ram horn peptone (RHP) using MO-1, a local isolate in submerged culture. First, a novel gram-negative and rod-shaped bacterial strain, MO-1, was isolated from the body of the grasshopper (Poecilemon tauricola Ramme 1951), which was collected from pesticide-contaminated fields. Sequence analysis of 16S rDNA classified the microbe as Serratia marcescens. The substrate utilization potential (BIOLOG) and fatty acid methyl ester profile (FAME) of S. marcescens were also determined. The effect of RHP on the production of prodigiosin by S. marcescens MO-1 was investigated, and the results showed that RHP supplementation promoted the growth of MO-1 and increased the production of prodigiosin. A concentration of 0.4% (w/v) RHP resulted in the greatest yield of prodigiosin (277.74 mg/L) after 48 h when mannitol was used as the sole source of carbon. The pigment yield was also influenced by the types of carbon sources and peptones. As a result, RHP was demonstrated to be a suitable substrate for prodigiosin production. These results revealed that prodigiosin could be produced efficiently by S. marcescens using RHP.(AU)
Assuntos
Animais , Meios de Cultura/química , Peptonas/metabolismo , Prodigiosina/metabolismo , Serratia marcescens/crescimento & desenvolvimento , Serratia marcescens/metabolismo , Técnicas de Tipagem Bacteriana , Análise por Conglomerados , Citosol/química , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Ribossômico/química , DNA Ribossômico/genética , Ácidos Graxos/análise , Gafanhotos/microbiologia , Dados de Sequência Molecular , Filogenia , Pigmentos Biológicos/metabolismo , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Serratia marcescens/classificação , Serratia marcescens/isolamento & purificaçãoRESUMO
Prodigiosin is a secondary metabolite produced by Serratia marcercens. As this pigment is suggested to be a cancer drug, genotoxicity studies are necessary. The aim of the present investigation was to evaluate the genotoxic effects of prodigiosin on tumoral and normal cell lines, NCIH-292, MCF-7 and HL-60. A normal line BGMK was used as control. Genomic damage induced by prodigiosin was observed in all tumor lines as well as the control line. The pigment induced the formation of micronuclei in tumor cells. The present data confirm the antitumor potential of prodigiosin. However, these findings also raise concerns regarding its target-specific action, as genotoxic effects on normal cells also occurred.
Assuntos
Dano ao DNA/efeitos dos fármacos , Genoma Humano/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Prodigiosina/administração & dosagem , Humanos , Células MCF-7 , Neoplasias/patologia , Prodigiosina/efeitos adversos , Serratia/química , Serratia/patogenicidade , Infecções por Serratia/complicações , Infecções por Serratia/tratamento farmacológico , Infecções por Serratia/genéticaRESUMO
BACKGROUND: The adapted arcometer has been validated for use in adults. However, its suitability for use in children can be questioned given the structural differences present in these populations. OBJECTIVE: To verify the concurrent validity, repeatability, and intra- and inter-reproducibility of the adapted arcometer for the measurement of the angles of thoracic kyphosis and lumbar lordosis in children. METHOD: Forty children were evaluated using both sagittal radiography of the spine and the adapted arcometer. The evaluations using the arcometer were carried out by two trained evaluators on two different days. In the statistical treatment, the intraclass correlation coefficient (ICC), Pearson's product moment correlation, Spearman's rho, the paired t test, and Wilcoxon's test were used (α=.05). RESULTS: A moderate and significant correlation was found between the x-ray and the adapted arcometer regarding thoracic kyphosis, but no correlation was found regarding lumbar lordosis. Repeatability and intra-evaluator reproducibility of the thoracic kyphosis and lumbar lordosis were confirmed, which was not the case of inter-evaluator reproducibility. CONCLUSION: The adapted arcometer can be used to accompany postural alterations in children made by the same evaluator, while its use for diagnostic purposes and continued evaluation by different evaluators cannot be recommended. Further studies with the aim of adapting this instrument for use in children are recommended. .