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1.
Molecules ; 28(13)2023 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-37446619

RESUMO

Steroidal (glycol)alkaloids S(G)As are secondary metabolites made of a nitrogen-containing steroidal skeleton linked to a (poly)saccharide, naturally occurring in the members of the Solanaceae and Liliaceae plant families. The genus Solanum is familiar to all of us as a food source (tomato, potato, eggplant), but a few populations have also made it part of their ethnobotany for their medicinal properties. The recent development of the isolation, purification and analysis techniques have shed light on the structural diversity among the SGAs family, thus attracting scientists to investigate their various pharmacological properties. This review aims to overview the recent literature (2012-2022) on the pharmacological benefits displayed by the SGAs family. Over 17 different potential therapeutic applications (antibiotic, antiviral, anti-inflammatory, etc.) were reported over the past ten years, and this unique review analyzes each pharmacological effect independently without discrimination of either the SGA's chemical identity or their sources. A strong emphasis is placed on the discovery of their biological targets and the subsequent cellular mechanisms, discussing in vitro to in vivo biological data. The therapeutic value and the challenges of the solanum steroidal glycoalkaloid family is debated to provide new insights for future research towards clinical development.


Assuntos
Alcaloides , Saúde da População , Solanum lycopersicum , Solanum nigrum , Solanum tuberosum , Solanum , Humanos , Solanum/metabolismo , Alcaloides/química , Solanum tuberosum/metabolismo , Solanum nigrum/metabolismo
2.
Artigo em Inglês | MEDLINE | ID: mdl-29610201

RESUMO

Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of deadly hospital-acquired infections. The discovery of anti-Staphylococcus antibiotics and new classes of drugs not susceptible to the mechanisms of resistance shared among bacteria is imperative. We recently showed that tomatidine (TO), a steroidal alkaloid from solanaceous plants, possesses potent antibacterial activity against S. aureus small-colony variants (SCVs), the notoriously persistent form of this bacterium that has been associated with recurrence of infections. Here, using genomic analysis of in vitro-generated TO-resistant S. aureus strains to identify mutations in genes involved in resistance, we identified the bacterial ATP synthase as the cellular target. Sequence alignments were performed to highlight the modified sequences, and the structural consequences of the mutations were evaluated in structural models. Overexpression of the atpE gene in S. aureus SCVs or introducing the mutation found in the atpE gene of one of the high-level TO-resistant S. aureus mutants into the Bacillus subtilis atpE gene provided resistance to TO and further validated the identity of the cellular target. FC04-100, a TO derivative which also possesses activity against non-SCV strains, prevents high-level resistance development in prototypic strains and limits the level of resistance observed in SCVs. An ATP synthesis assay allowed the observation of a correlation between antibiotic potency and ATP synthase inhibition. The selectivity index (inhibition of ATP production by mitochondria versus that of bacterial ATP synthase) is estimated to be >105-fold for FC04-100.


Assuntos
Antibacterianos/farmacologia , ATPases Mitocondriais Próton-Translocadoras/química , ATPases Mitocondriais Próton-Translocadoras/metabolismo , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/enzimologia , Tomatina/análogos & derivados , Bacillus subtilis/efeitos dos fármacos , Bacillus subtilis/metabolismo , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/metabolismo , Testes de Sensibilidade Microbiana , ATPases Mitocondriais Próton-Translocadoras/genética , Mutação , Tomatina/farmacologia
3.
Antimicrob Agents Chemother ; 59(12): 7458-64, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26392496

RESUMO

This study investigated the antibacterial activity of the plant alkaloid tomatidine (TO) against Staphylococcus aureus grown in the presence of Pseudomonas aeruginosa. Since the P. aeruginosa exoproduct 4-hydroxy-2-heptylquinoline-N-oxide (HQNO) is known to cause a respiratory deficiency in S. aureus and respiratory-deficient S. aureus are known to be hypersensitive to TO, we assessed kill kinetics of TO (8 µg/ml) against S. aureus in coculture with P. aeruginosa. Kill kinetics were also assessed using P. aeruginosa mutants deficient in the production of different exoproducts and quorum sensing-related compounds. After 24 h in coculture, TO increased the killing of S. aureus by 3.4 log10 CFU/ml in comparison to that observed in a coculture without TO. The effect of TO was abolished when S. aureus was in coculture with the lasR rhlR, pqsA, pqsL, or lasA mutant of P. aeruginosa. The bactericidal effect of TO against S. aureus in coculture with the pqsL mutant was restored by supplemental HQNO. In an S. aureus monoculture, the combination of HQNO and TO was bacteriostatic, indicating that the pqsL mutant produced an additional factor required for the bactericidal effect. The bactericidal activity of TO was also observed against a tobramycin-resistant methicillin-resistant S. aureus (MRSA) in coculture with P. aeruginosa, and the addition of tobramycin significantly suppressed the growth of both microorganisms. TO shows a strong bactericidal effect against S. aureus when cocultured with P. aeruginosa. The combination of TO and tobramycin may represent a new treatment approach for cystic fibrosis patients frequently cocolonized by MRSA and P. aeruginosa.


Assuntos
Antibacterianos/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos , Tobramicina/farmacologia , Tomatina/análogos & derivados , Proteínas de Bactérias/genética , Técnicas de Cocultura , Sinergismo Farmacológico , Hidroxiquinolinas/metabolismo , Metaloproteases/genética , Testes de Sensibilidade Microbiana , Mutação , Pseudomonas aeruginosa/genética , Percepção de Quorum , Tomatina/farmacologia , Transativadores/genética , Fatores de Virulência/genética
4.
PLoS Pathog ; 9(6): e1003435, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23785291

RESUMO

RNA silencing mediated by small RNAs (sRNAs) is a conserved regulatory process with key antiviral and antimicrobial roles in eukaryotes. A widespread counter-defensive strategy of viruses against RNA silencing is to deploy viral suppressors of RNA silencing (VSRs), epitomized by the P19 protein of tombusviruses, which sequesters sRNAs and compromises their downstream action. Here, we provide evidence that specific Nicotiana species are able to sense and, in turn, antagonize the effects of P19 by activating a highly potent immune response that protects tissues against Tomato bushy stunt virus infection. This immunity is salicylate- and ethylene-dependent, and occurs without microscopic cell death, providing an example of "extreme resistance" (ER). We show that the capacity of P19 to bind sRNA, which is mandatory for its VSR function, is also necessary to induce ER, and that effects downstream of P19-sRNA complex formation are the likely determinants of the induced resistance. Accordingly, VSRs unrelated to P19 that also bind sRNA compromise the onset of P19-elicited defense, but do not alter a resistance phenotype conferred by a viral protein without VSR activity. These results show that plants have evolved specific responses against the damages incurred by VSRs to the cellular silencing machinery, a likely necessary step in the never-ending molecular arms race opposing pathogens to their hosts.


Assuntos
Resistência à Doença/fisiologia , Nicotiana/metabolismo , Interferência de RNA/fisiologia , RNA de Plantas/metabolismo , Tombusvirus/metabolismo , Proteínas Virais/metabolismo , Morte Celular/genética , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/metabolismo , Plantas Geneticamente Modificadas/virologia , Ligação Proteica , RNA de Plantas/genética , Nicotiana/genética , Nicotiana/virologia , Tombusvirus/genética , Proteínas Virais/genética
5.
Plant Cell ; 24(2): 762-77, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22374398

RESUMO

Auxin is a pivotal plant hormone that regulates many aspects of plant growth and development. Auxin signaling is also known to promote plant disease caused by plant pathogens. However, the mechanism by which this hormone confers susceptibility to pathogens is not well understood. Here, we present evidence that fungal and bacterial plant pathogens hijack the host auxin metabolism in Arabidopsis thaliana, leading to the accumulation of a conjugated form of the hormone, indole-3-acetic acid (IAA)-Asp, to promote disease development. We also show that IAA-Asp increases pathogen progression in the plant by regulating the transcription of virulence genes. These data highlight a novel mechanism to promote plant susceptibility to pathogens through auxin conjugation.


Assuntos
Arabidopsis/microbiologia , Ácido Aspártico/metabolismo , Interações Hospedeiro-Patógeno , Ácidos Indolacéticos/metabolismo , Doenças das Plantas/microbiologia , Transdução de Sinais , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Ácido Aspártico/farmacologia , Botrytis/patogenicidade , Ciclopentanos/metabolismo , Regulação da Expressão Gênica de Plantas , Ácidos Indolacéticos/farmacologia , Indóis/metabolismo , Oxilipinas/metabolismo , Reguladores de Crescimento de Plantas/metabolismo , Reguladores de Crescimento de Plantas/farmacologia , Pseudomonas syringae/patogenicidade , Ácido Salicílico/metabolismo , Tiazóis/metabolismo , Virulência
6.
Plant Cell ; 23(6): 2405-21, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21665999

RESUMO

Plants have evolved sophisticated mechanisms to sense and respond to pathogen attacks. Resistance against necrotrophic pathogens generally requires the activation of the jasmonic acid (JA) signaling pathway, whereas the salicylic acid (SA) signaling pathway is mainly activated against biotrophic pathogens. SA can antagonize JA signaling and vice versa. Here, we report that the necrotrophic pathogen Botrytis cinerea exploits this antagonism as a strategy to cause disease development. We show that B. cinerea produces an exopolysaccharide, which acts as an elicitor of the SA pathway. In turn, the SA pathway antagonizes the JA signaling pathway, thereby allowing the fungus to develop its disease in tomato (Solanum lycopersicum). SA-promoted disease development occurs through Nonexpressed Pathogen Related1. We also show that the JA signaling pathway required for tomato resistance against B. cinerea is mediated by the systemin elicitor. These data highlight a new strategy used by B. cinerea to overcome the plant's defense system and to spread within the host.


Assuntos
Botrytis/patogenicidade , Imunidade Inata/imunologia , Doenças das Plantas/imunologia , Doenças das Plantas/microbiologia , Transdução de Sinais/imunologia , Solanum lycopersicum/imunologia , Solanum lycopersicum/microbiologia , Anti-Infecciosos , Botrytis/metabolismo , Configuração de Carboidratos , Ciclopentanos/metabolismo , Defensinas/genética , Defensinas/metabolismo , Glucanos/química , Glucanos/metabolismo , Solanum lycopersicum/genética , Dados de Sequência Molecular , Oxilipinas/metabolismo , Folhas de Planta/imunologia , Folhas de Planta/microbiologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas , Ácido Salicílico/metabolismo
7.
Mol Plant Microbe Interact ; 25(12): 1584-93, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22950753

RESUMO

Plants use different immune pathways to combat pathogens. The activation of the jasmonic acid (JA)-signaling pathway is required for resistance against necrotrophic pathogens; however, to combat biotrophic pathogens, the plants activate mainly the salicylic acid (SA)-signaling pathway. SA can antagonize JA signaling and vice versa. NPR1 (noninducible pathogenesis-related 1) is considered a master regulator of SA signaling. NPR1 interacts with TGA transcription factors, ultimately leading to the activation of SA-dependent responses. SA has been shown to promote disease development caused by the necrotrophic pathogen Botrytis cinerea through NPR1, by suppressing the expression of two JA-dependent defense genes, proteinase inhibitors I and II. We show here that the transcription factor TGA1.a contributes to disease development caused by B. cinerea in tomato by suppressing the expression of proteinase inhibitors I and II. Finally, we present evidence that the SA-signaling pathway contributes to disease development caused by another necrotrophic pathogen, Alternaria solani, in tomato. Disease development promoted by SA through NPR1 requires the TGA1.a transcription factor. These data highlight how necrotrophs manipulate the SAsignaling pathway to promote their disease in tomato.


Assuntos
Alternaria/patogenicidade , Botrytis/patogenicidade , Doenças das Plantas/microbiologia , Ácido Salicílico/metabolismo , Transdução de Sinais , Solanum lycopersicum/microbiologia , Ciclopentanos/antagonistas & inibidores , Ciclopentanos/metabolismo , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Interações Hospedeiro-Patógeno , Solanum lycopersicum/genética , Solanum lycopersicum/fisiologia , Modelos Biológicos , Oxilipinas/antagonistas & inibidores , Oxilipinas/metabolismo , Reguladores de Crescimento de Plantas/metabolismo , Imunidade Vegetal , Folhas de Planta/genética , Folhas de Planta/microbiologia , Folhas de Planta/fisiologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Inibidores de Proteases , Ácido Salicílico/farmacologia , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
8.
J Antimicrob Chemother ; 67(3): 559-68, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22129590

RESUMO

OBJECTIVES: This study characterized the multiple biological activities of the natural compound tomatidine against Staphylococcus aureus. Notably, this work examined the antibacterial activity of tomatidine in combination with other antibiotics and the influence of this compound on the expression of virulence factors in S. aureus. METHODS: The effect of tomatidine on the susceptibility of S. aureus to several antibiotic classes was determined by a broth microdilution procedure and a chequerboard protocol to measure fractional inhibitory concentration indices and to reveal drug interactions. Time-kill experiments for aminoglycoside/tomatidine combinations were also performed. The haemolytic ability of several strains in the presence of tomatidine was measured on blood agar plates and the expression of virulence-associated genes in strain ATCC 29213 treated with tomatidine was monitored by quantitative PCR. RESULTS: Tomatidine specifically potentiated the inhibitory effect of aminoglycosides but not of other classes of drugs. This potentiating effect was observed against strains of different clinical origins (human blood, cystic fibrosis airways, osteomyelitis, skin tissues and bovine mastitis), including aminoglycoside-resistant bacteria possessing the aac(6')-aph(2″), ant(4')-Ia and aph(3')-IIIa genes. The killing kinetics for the combination of aminoglycosides with tomatidine revealed strong bactericidal activity. Although tomatidine did not possess growth-inhibitory activity of its own against prototypical S. aureus, it inhibited the haemolytic activity of several strains and, more specifically, blocked the expression of several genes normally influenced by the agr system. CONCLUSIONS: These results show that tomatidine is an aminoglycoside potentiator that also acts as an anti-virulence agent targeting both antibiotic-susceptible and antibiotic-resistant S. aureus.


Assuntos
Aminoglicosídeos/farmacologia , Antibacterianos/farmacologia , Sinergismo Farmacológico , Staphylococcus aureus/efeitos dos fármacos , Tomatina/análogos & derivados , Fatores de Virulência/antagonistas & inibidores , Animais , Meios de Cultura/química , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Eritrócitos/microbiologia , Perfilação da Expressão Gênica , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Proteínas Hemolisinas/antagonistas & inibidores , Hemólise , Cavalos , Testes de Sensibilidade Microbiana , Viabilidade Microbiana/efeitos dos fármacos , Reação em Cadeia da Polimerase em Tempo Real , Staphylococcus aureus/patogenicidade , Fatores de Tempo , Tomatina/farmacologia , Virulência
10.
Antimicrob Agents Chemother ; 55(5): 1937-45, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21357296

RESUMO

Small-colony variants (SCVs) often are associated with chronic Staphylococcus aureus infections, such as those encountered by cystic fibrosis (CF) patients. We report here that tomatidine, the aglycon form of the plant secondary metabolite tomatine, has a potent growth inhibitory activity against SCVs (MIC of 0.12 µg/ml), whereas the growth of normal S. aureus strains was not significantly altered by tomatidine (MIC, >16 µg/ml). The specific action of tomatidine was bacteriostatic for SCVs and was clearly associated with their dysfunctional electron transport system, as the presence of the electron transport inhibitor 4-hydroxy-2-heptylquinoline-N-oxide (HQNO) caused normal S. aureus strains to become susceptible to tomatidine. Inversely, the complementation of SCVs' respiratory deficiency conferred resistance to tomatidine. Tomatidine provoked a general reduction of macromolecular biosynthesis but more specifically affected the incorporation of radiolabeled leucine in proteins of HQNO-treated S. aureus at a concentration corresponding to the MIC against SCVs. Furthermore, tomatidine inhibited the intracellular replication of a clinical SCV in polarized CF-like epithelial cells. Our results suggest that tomatidine eventually will find some use in combination therapy with other traditional antibiotics to eliminate persistent forms of S. aureus.


Assuntos
Fibrose Cística/complicações , Fibrose Cística/microbiologia , Staphylococcus aureus/efeitos dos fármacos , Tomatina/análogos & derivados , Linhagem Celular , Gentamicinas/farmacologia , Humanos , Hidroxiquinolinas/farmacologia , Testes de Sensibilidade Microbiana , Microscopia de Fluorescência , Estrutura Molecular , Infecções Estafilocócicas/microbiologia , Tomatina/farmacologia
11.
Environ Microbiol ; 12(1): 239-53, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19799622

RESUMO

To protect themselves, plants have evolved an armoury of defences in response to pathogens and other stress situations. These include the production of pathogenesis-related (PR) proteins and the accumulation of antimicrobial molecules such as phytoalexins. Here we report that resistance of tobacco to Botrytis cinerea is cultivar specific. Nicotiana tabacum cv. Petit Havana but not N. tabacum cv. Xanthi or cv. samsun is resistant to B. cinerea. This resistance is correlated with the accumulation of the phytoalexin scopoletin and PR proteins. We also show that this resistance depends on the type of B. cinerea stage. Nicotiana tabacum cv. Petit Havana is more resistant to spores than to mycelium of B. cinerea. This reduced resistance of N. tabacum cv. Petit Havana to the mycelium compared with spores is correlated with the suppression of PR proteins accumulation and the capacity of the mycelium, not the spores, to metabolize scopoletin. These data present an important advance in understanding the strategies used by B. cinerea to establish its disease on tobacco plants.


Assuntos
Botrytis/patogenicidade , Nicotiana/microbiologia , Doenças das Plantas/genética , Proteínas de Plantas/metabolismo , Escopoletina/metabolismo , Botrytis/metabolismo , Regulação da Expressão Gênica de Plantas , Imunidade Inata , Micélio/metabolismo , Micélio/patogenicidade , Doenças das Plantas/imunologia , Doenças das Plantas/microbiologia , Proteínas de Plantas/genética , Proteínas de Plantas/imunologia , Escopoletina/imunologia , Esporos Fúngicos/metabolismo , Esporos Fúngicos/patogenicidade , Nicotiana/genética , Nicotiana/imunologia
12.
Pathogens ; 9(10)2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33007866

RESUMO

Siderophores produced in soil by plant growth-promoting rhizobacteria (PGPRs) play several roles, including nutrient mobilizers and can be useful as plants defense elicitors. We investigated the role of a synthetic mixed ligand bis-catechol-mono-hydroxamate siderophore (SID) that mimics the chemical structure of a natural siderophore, fimsbactin, produced by Acinetobacter spp. in the resistance against the phytopathogen Pseudomonas syringaepv tomato DC3000 (Pst DC3000), in Arabidopsis thaliana. We first tested the antibacterial activity of SID against Pst DC3000 in vitro. After confirming that SID had antibacterial activity against Pst DC3000, we tested whether the observed in vitro activity could translate into resistance of Arabidopsis to Pst DC3000, using bacterial loads as endpoints in a plant infection model. Furthermore, using quantitative polymerase chain reaction, we explored the molecular actors involved in the resistance of Arabidopsis induced by SID. Finally, to assure that SID would not interfere with PGPRs, we tested in vitro the influence of SID on the growth of a reference PGPR, Bacillus subtilis. We report here that SID is an antibacterial agent as well as an inducer of systemic priming of resistance in A. thaliana against Pst DC3000, and that SID can, at the same time, promote growth of a PGPR.

13.
Front Microbiol ; 11: 805, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32431678

RESUMO

Tomatidine (TO), a steroid alkaloid, exerts a strong bactericidal activity on the infection-persistent phenotype of Staphylococcus aureus, the small-colony variant (SCV), with a minimal inhibitory concentration (MIC) of 0.06 µg/ml. Also, the combination of TO to an aminoglycoside (AMG) shows a strong synergistic effect against prototypical (WT) S. aureus (MIC 0.06 µg/ml), which is otherwise unaffected by TO alone (MIC > 128 µg/ml). We have recently established that the ATP synthase (subunit AtpE) was the molecular target of TO and that TO reduces the production of ATP in S. aureus. The purpose of this study was to understand how TO and the TO-AMG combination exert bactericidal activities against S. aureus SCV and WT strains, respectively. The impact of TO and of the TO-gentamicin (GEN) combination on the membrane potential and generation of reactive oxygen species (ROS) were determined using florescent probes. GEN uptake in WT was assessed in the presence of TO. Virulence of SCV and WT strains as well as of in vitro-selected mutants showing resistance to TO or the TO-GEN combination was evaluated in a murine thigh infection model. TO causes a reduction in membrane potential in both WT and SCV, but significant amounts of ROS are only produced in SCVs. Besides, the presence of TO improves the uptake of GEN by the WT strain and the combination TO-GEN generated 2.5-folds more ROS in WT, compared to that induced by GEN alone. Under anaerobic conditions, WT adopts a fermentative slow-growth phenotype and becomes susceptible to TO even if used alone. In vivo, TO- or TO-GEN-resistant strains were significantly altered in their ability to colonize tissues. These results shed light on the mechanism of action of TO and its synergy with AMGs against S. aureus WT. TO bactericidal activity against SCVs is attributable to both a critical drop in the membrane potential accompanied by a substantial ROS production. In the WT, TO helps GEN uptake and ROS is also important for the synergy. Acquiring resistance to TO significantly impairs virulence. The residual ATP synthase activity of SCVs might represent the Achilles' heel of persistent S. aureus.

14.
Plant Cell Rep ; 28(12): 1895-903, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19859716

RESUMO

Streptomyces scabiei is the predominant causal agent of common scab of potato in North America. The virulence of common scab-causing streptomycetes relies on their capacity to synthesize thaxtomins. In this study, the effects of S. scabiei infection and of thaxtomin A, the main toxin produced by S. scabiei, were tested for the elicitation of plant defense molecules in the model plants tobacco (Nicotiana tabacum) and Arabidopsis thaliana. Tobacco leaves infected with spores of S. scabiei strain EF-35 or infiltrated with purified thaxtomin A produced a blue fluorescent compound that was not detected in leaves infiltrated with spores of a S. scabiei mutant deficient in thaxtomin A biosynthesis. Thin layer chromatography and high performance liquid chromatography identified this fluorescent compound as scopoletin, a plant defense phytoalexin. Arabidopsis seedlings grown in liquid medium also excreted scopoletin as a reaction to S. scabiei and thaxtomin A. The effects of the presence of scopoletin on S. scabiei were also investigated. The phytoalexin scopoletin caused a slight reduction of bacterial growth and a severe decrease of thaxtomin A production. Scopoletin was shown to inhibit thaxtomin A production by repression of a gene involved in the toxin biosynthesis.


Assuntos
Arabidopsis/metabolismo , Arabidopsis/microbiologia , Toxinas Bacterianas/farmacologia , Indóis/farmacologia , Nicotiana/microbiologia , Piperazinas/farmacologia , Escopoletina/metabolismo , Streptomyces/fisiologia , Anti-Infecciosos/farmacologia , Arabidopsis/efeitos dos fármacos , Arabidopsis/crescimento & desenvolvimento , Espaço Extracelular/efeitos dos fármacos , Espaço Extracelular/metabolismo , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Genes Bacterianos/genética , Indóis/metabolismo , Piperazinas/metabolismo , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/metabolismo , Sesquiterpenos , Streptomyces/efeitos dos fármacos , Streptomyces/genética , Streptomyces/crescimento & desenvolvimento , Terpenos/metabolismo , Nicotiana/efeitos dos fármacos , Nicotiana/metabolismo , Fitoalexinas
15.
Int J Mol Sci ; 10(8): 3400-3419, 2009 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-20111686

RESUMO

To protect themselves, plants accumulate an armoury of antimicrobial secondary metabolites. Some metabolites represent constitutive chemical barriers to microbial attack (phytoanticipins) and others inducible antimicrobials (phytoalexins). They are extensively studied as promising plant and human disease-controlling agents. This review discusses the bioactivity of several phytoalexins and phytoanticipins defending plants against fungal and bacterial aggressors and those with antibacterial activities against pathogens affecting humans such as Pseudomonas aeruginosa and Staphylococcus aureus involved in respiratory infections of cystic fibrosis patients. The utility of plant products as "antibiotic potentiators" and "virulence attenuators" is also described as well as some biotechnological applications in phytoprotection.


Assuntos
Anti-Infecciosos/química , Plantas/química , Anti-Infecciosos/farmacologia , Humanos , Plantas/metabolismo , Pseudomonas aeruginosa/efeitos dos fármacos , Saponinas/química , Saponinas/farmacologia , Sesquiterpenos/química , Sesquiterpenos/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Fitoalexinas
16.
BMC Pharmacol Toxicol ; 19(1): 7, 2018 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-29439722

RESUMO

BACKGROUND: Tomatidine (TO) is a plant steroidal alkaloid that possesses an antibacterial activity against the small colony variants (SCVs) of Staphylococcus aureus. We report here the spectrum of activity of TO against other species of the Bacillales and the improved antibacterial activity of a chemically-modified TO derivative (FC04-100) against Listeria monocytogenes and antibiotic multi-resistant S. aureus (MRSA), two notoriously difficult-to-kill microorganisms. METHODS: Bacillus and Listeria SCVs were isolated using a gentamicin selection pressure. Minimal inhibitory concentrations (MICs) of TO and FC04-100 were determined by a broth microdilution technique. The bactericidal activity of TO and FC04-100 used alone or in combination with an aminoglycoside against planktonic bacteria was determined in broth or against bacteria embedded in pre-formed biofilms by using the Calgary Biofilm Device. Killing of intracellular SCVs was determined in a model with polarized pulmonary cells. RESULTS: TO showed a bactericidal activity against SCVs of Staphylococcus aureus, Bacillus cereus, B. subtilis and Listeria monocytogenes with MICs of 0.03-0.12 µg/mL. The combination of an aminoglycoside and TO generated an antibacterial synergy against their normal phenotype. In contrast to TO, which has no relevant activity by itself against Bacillales of the normal phenotype (MIC > 64 µg/mL), the TO analog FC04-100 showed a MIC of 8-32 µg/mL. Furthermore, FC04-100 showed a strong bactericidal activity against L. monocytogenes SCVs in kill kinetics experiments, while TO did not. The addition of FC04-100 (4 µg/mL) to a cefalexin:kanamycin (3:2) combination improved the activity of the combination by 32 fold against cefalexin and kanamycin-resistant MRSA strains. In combination with gentamicin, FC04-100 also exhibited a strong bactericidal activity against biofilm-embedded S. aureus. Also, FC04-100 and TO showed comparable intracellular killing of S. aureus SCVs. CONCLUSIONS: Chemical modifications of TO allowed improvement of its antibacterial activity against prototypical S. aureus and of its bactericidal activity against L. monocytogenes. Antibacterial activities against such prominent pathogens could be useful to prevent Listeria contamination in the food chain or as treatment for MRSA infections.


Assuntos
Antibacterianos/farmacologia , Bacillales/efeitos dos fármacos , Tomatina/análogos & derivados , Bacillales/crescimento & desenvolvimento , Farmacorresistência Bacteriana , Testes de Sensibilidade Microbiana , Tomatina/farmacologia
17.
Curr Opin Plant Biol ; 5(4): 308-17, 2002 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12179964

RESUMO

Marine algae encompass lineages that diverged about one billion years ago. Recent results suggest that they feature natural immunity traits that are conserved, as well as others that appear to be phylum- or environment-specific. In particular, marine plants resemble terrestrial plants and animals in their basic mechanisms for pathogen recognition and signaling, suggesting that these essential cell functions arose in the sea. Specific traits are based on the synthesis of unique secondary defense metabolites, often making use of the variety of halides found in the sea.


Assuntos
Eucariotos/fisiologia , Eucariotos/classificação , Eucariotos/genética , Expressão Gênica , Halogênios/metabolismo , Imunidade Inata/fisiologia , Biologia Marinha , Filogenia , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/fisiologia , Estresse Mecânico
18.
Eur J Med Chem ; 80: 605-20, 2014 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-24877760

RESUMO

Staphylococcus aureus (S. aureus) is responsible for difficult-to-treat and relapsing infections and constitutes one of the most problematic pathogens due to its multiple resistances to clinically available antibiotics. Additionally, the ability of S. aureus to develop small-colony variants is associated with a reduced susceptibility to aminoglycoside antibiotics and in vivo persistence. We have recently demonstrated that tomatidine, a steroid alkaloid isolated from tomato plants, possesses anti-virulence activity against normal strains of S. aureus as well as the ability to potentiate the effect of aminoglycoside antibiotics. In addition, tomatidine has shown antibiotic activity against small-colony variants of S. aureus. We herein report the first study of the structure-activity relationship of tomatidine against S. aureus.


Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Tomatina/análogos & derivados , Testes de Sensibilidade Microbiana , Staphylococcus aureus/crescimento & desenvolvimento , Relação Estrutura-Atividade , Tomatina/química , Tomatina/farmacologia
19.
Plant Cell ; 20(11): 3136-47, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19028963

RESUMO

Transcriptional reprogramming is critical for plant disease resistance responses. In potato (Solanum tuberosum), the marker gene PATHOGENESIS-RELATED-10a (PR-10a) is transcriptionally activated by pathogens, wounding, or elicitor treatment. Activation of PR-10a requires the recruitment of the activator Why1 to its promoter. In addition, PR-10a is negatively regulated by the repressor SEBF (for Silencer Element Binding Factor). Here, we show through a yeast two-hybrid screen that SEBF interacts with Pti4, which has been shown to be a transcriptional activator. SEBF recruits Pti4 via its consensus sequence-type RNA binding domain, while Pti4 is recruited to SEBF by means of its ethylene-response factor domain. In vivo plant transcription assays confirmed that SEBF interacts with Pti4 to form a repressosome, showing that Pti4 can also play a role in transcriptional repression. Chromatin immunoprecipitation revealed that both SEBF and Pti4 are recruited to the PR-10a promoter in uninduced conditions only and that the recruitment of Pti4 is dependent on the presence of SEBF, consistent with the fact that there is no Pti4 consensus binding site in PR-10a. Unexpectedly, we also demonstrated that recruitment of SEBF was dependent on the presence of Pti4, thereby explaining why SEBF, itself a repressor, requires Pti4 for its repressing function.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Proteínas de Plantas/metabolismo , Proteínas Repressoras/metabolismo , Solanum tuberosum/genética , Ativação Transcricional , Imunoprecipitação da Cromatina , Proteínas de Ligação a DNA/genética , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Dados de Sequência Molecular , Proteínas de Plantas/genética , Regiões Promotoras Genéticas , RNA de Plantas/genética , Proteínas Repressoras/genética , Solanum tuberosum/metabolismo , Técnicas do Sistema de Duplo-Híbrido
20.
New Phytol ; 175(1): 131-139, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17547673

RESUMO

* Botrytis cinerea is a necrotrophic fungus that causes grey mould on a wide range of food plants, especially grapevine, tomato, soft fruits and vegetables. This disease brings about important economic losses in both pre- and postharvest crops. Successful protection of host plants against this pathogen is severely hampered by a lack of resistance genes in the hosts and the considerable phenotypic diversity of the fungus. * The aim of this study was to test whether B. cinerea manipulates the immunity-signalling pathways in plants to restore its disease. * We showed that B. cinerea caused disease in Nicotiana benthamiana through the activation of two plant signalling genes, EDS1 and SGT1, which have been shown to be essential for resistance against biotrophic pathogens; and more interestingly, virus-induced gene silencing of these two plant signalling components enhanced N. benthamiana resistance to B. cinerea. Finally, plants expressing the baculovirus antiapoptotic protein p35 were more resistant to this necrotrophic pathogen than wild-type plants. * This work highlights a new strategy used by B. cinerea to establish disease. This information is important for the design of strategies to improve plant pathogen resistance.


Assuntos
Botrytis/patogenicidade , Proteínas de Ligação a DNA/metabolismo , Glucosiltransferases/metabolismo , Nicotiana/fisiologia , Nicotiana/virologia , Doenças das Plantas/microbiologia , Proteínas de Plantas/metabolismo , Transdução de Sinais/fisiologia , Baculoviridae/patogenicidade , Primers do DNA , Proteínas de Ligação a DNA/genética , Glucosiltransferases/genética , Doenças das Plantas/virologia , Folhas de Planta/microbiologia , Folhas de Planta/fisiologia , Folhas de Planta/virologia , Proteínas de Plantas/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa
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