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1.
Ecotoxicol Environ Saf ; 187: 109823, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31639641

RESUMO

Time-dependent cross-phenomenon in which the cross between the actual concentration-response curve (CRC) for mixture crosses the CRCs for reference model varies with time has been frequently reported in previous studies, expressed as a heterogeneous pattern of joint toxic action. However, the variation tendency of time-dependent cross-phenomenon is rarely addressed. In this study, the joint toxic actions of binary antibacterial mixtures (i.e., two quorum sensing inhibitors, tetracycline hydrochloride, erythromycin, and chloramphenicol with sulfonamides) were judged using independent action (IA) model to find the variation tendency of time-dependent cross-phenomenon. The results show that the time-dependent cross-phenomena of the test binary antibacterial mixtures follow a unified variation tendency and the corresponding joint toxic actions change regularly with an increase of both concentration and time. Through investigating the relationship between the stimulatory and inhibitory modes of action for the single agents and the time-dependent cross-phenomena of binary mixtures, the regular time-dependent cross-phenomena is speculated to be derived from the hormetic effects of the components in the mixtures. This study offers an advance for the variation tendency and mechanistic explanation of time-dependent cross-phenomenon, which will provide a support for the future development in the exploration of time-dependent cross-phenomenon and environmental risk assessment of pollutant mixtures.


Assuntos
Aliivibrio fischeri/efeitos dos fármacos , Antibacterianos/toxicidade , Poluentes Ambientais/toxicidade , Hormese , Aliivibrio fischeri/metabolismo , Antibacterianos/farmacocinética , Misturas Complexas/farmacocinética , Misturas Complexas/toxicidade , Poluentes Ambientais/farmacocinética , Modelos Biológicos , Percepção de Quorum/efeitos dos fármacos , Fatores de Tempo
2.
Food Microbiol ; 86: 103356, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31703863

RESUMO

Quorum sensing (QS), bacterial cell-to-cell communication, is a gene regulatory mechanism that regulates virulence potential and biofilm formation in many pathogens. Aeromonas sobria, a common aquaculture pathogen, was isolated and identified by our laboratory from the deteriorated turbot, and its potential for virulence factors and biofilm production was regulated by QS system. In view of the interference with QS system, this study was aimed to investigate the effect of methyl anthranilate at sub-Minimum Inhibitory Concentrations (sub-MICs) on QS-regulated phenotypes in A. sobria. The results suggested that 0.5 µL/mL of methyl anthranilate evidently reduced biofilm formation (51.44%), swinging motility (74.86%), swarming motility (71.63%), protease activity (43.08%), and acyl-homoserine lactone (AHL) production. Furthermore, the real-time quantitative PCR (RT-qPCR) and in silico analysis showed that methyl anthranilate might inhibit QS system in A. sobria by interfering with the biosynthesis of AHL, as well as competitively binding with receptor protein. Therefore, our data indicated the feasibility of methyl anthranilate as a promising QS inhibitor and anti-biofilm agent for improving food safety.


Assuntos
Aeromonas/efeitos dos fármacos , Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Percepção de Quorum/efeitos dos fármacos , ortoaminobenzoatos/farmacologia , 4-Butirolactona/análogos & derivados , 4-Butirolactona/metabolismo , Aeromonas/genética , Aeromonas/fisiologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Fatores de Virulência/genética , Fatores de Virulência/metabolismo
3.
J Photochem Photobiol B ; 201: 111637, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31706086

RESUMO

Plants are considered to be a leading source for possible human therapeutic agents. This holistic study has investigated the anti-quorum sensing (anti-QS), anti-infection, antioxidant and anti-photoaging properties of neglected plant Diplocyclos palmatus. The results showed that D. palmatus methanolic leaf extract (DPME) effectively inhibited the quorum sensing (QS) regulated virulence factor production as well as biofilm formation in Serratia marcescens. The transcriptomic analysis revealed that DPME significantly downed the expression of QS-regulated genes such as fimA, fimC, flhC, bsmB, pigP and shlA in S. marcescens, which supports the outcome of in vitro bioassays. Further, the docking study revealed that the presence of active compounds, namely tocopherols and phytol, DPME exhibited its anti-QS activity against S. marcescens. In addition, DPME treatment extended the lifespan of S. marcescens infected C. elegans by the action of dropping the internal accumulation. Further, qPCR analysis clearly revealed that DPME treatment significantly up-regulated the expression of the lifespan-related gene (daf-16) and immune-related genes (clec-60, clec-87, lys-7 and bec-1) in S. marcescens infected C.elegans. On the other hand, DPME extensively reduced the UV-A induced ROS stress, thereby, extended the lifespan in UV-A photoaged C. elegans. Further, the qPCR analysis also confirmed the up-regulation of daf-16, clec-60, clec-87 and col-19 genes which advocated the improvement of the lifespan, healthspan and collagen production in UV-A photoaged C. elegans. Further bioassays evidenced that that the lifespan extension of photoaged C. elegans was accomplished by the actions of antioxidants such as tocopherols and phytol in DPME.


Assuntos
Envelhecimento/efeitos dos fármacos , Caenorhabditis elegans/efeitos da radiação , Cucurbitaceae/química , Extratos Vegetais/farmacologia , Percepção de Quorum/efeitos dos fármacos , Serratia marcescens/fisiologia , Raios Ultravioleta , Envelhecimento/efeitos da radiação , Animais , Antioxidantes/química , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Biofilmes/efeitos dos fármacos , Caenorhabditis elegans/efeitos dos fármacos , Caenorhabditis elegans/fisiologia , Colágeno/metabolismo , Cucurbitaceae/metabolismo , Longevidade/efeitos dos fármacos , Extratos Vegetais/química , Folhas de Planta/química , Folhas de Planta/metabolismo , Infecções por Serratia/patologia , Infecções por Serratia/veterinária , Regulação para Cima/efeitos dos fármacos
4.
Fitoterapia ; 139: 104405, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31707126

RESUMO

There is a continuing rise in the occurrence of multidrug-resistant bacterial infections. Antibiotic resistance to currently available antibiotics has become a global health issue leading to an urgent need for alternative antibacterial strategies. There has been a renewed interest in the development of antibacterial agents from natural sources, and trans-cinnamaldehyde is an example of a naturally occurring compound that has received significant attention in recent years. Trans-Cinnamaldehyde has been shown to possess substantial antimicrobial activity, as well as an array of other medicinal properties, and represents an intriguing hit compound from which a number of derivatives have been developed. In some cases, these derivatives have been shown to possess improved activity, not only compared to trans-cinnamaldehyde but also to commonly used antibiotics. Therefore, understanding the antibacterial mechanisms of action that these compounds elicit is imperative in order to facilitate their development and the development of new antibacterial agents that could exploit similar mechanistic approaches. The purpose of this review is to provide an overview of current knowledge on the antibacterial activity and mechanisms of action of cinnamaldehyde and its derivatives, and to highlight significant contributions made in this research area. It is hoped that the findings presented in this work will aid the future development of new antibacterial agents.


Assuntos
Acroleína/análogos & derivados , Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Percepção de Quorum/efeitos dos fármacos , Acroleína/química , Acroleína/farmacologia , Antibacterianos/química , Bactérias/efeitos dos fármacos , Cinnamomum/química , Estrutura Molecular , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Casca de Planta/química
5.
Chem Pharm Bull (Tokyo) ; 67(10): 1088-1098, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31582628

RESUMO

In this study, we synthesized four series of novel L-homoserine lactone analogs and evaluated their in vitro quorum sensing (QS) inhibitory activity against two biomonitor strains, Chromobacterium violaceum CV026 and Pseudomonas aeruginosa PAO1. Studies of the structure-activity relationships of the set of L-homoserine lactone analogs indicated that phenylurea-containing N-dithiocarbamated homoserine lactones are more potent than (Z)-4-bromo-5-(bromomethylene)-2(5H)-furanone (C30), a positive control for biofilm formation. In particular, compared with C30, QS inhibitor 11f significantly reduced the production of virulence factors (pyocyanin, elastase and rhamnolipid), swarming motility, the formation of biofilm and the mRNA level of QS-related genes regulated by the QS system of PAO1. These results reveal 11f as a potential lead compound for developing novel antibacterial quorum sensing inhibitors.


Assuntos
4-Butirolactona/análogos & derivados , Antibacterianos/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Percepção de Quorum/efeitos dos fármacos , 4-Butirolactona/síntese química , 4-Butirolactona/química , 4-Butirolactona/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Estrutura Molecular , Pseudomonas aeruginosa/crescimento & desenvolvimento , Percepção de Quorum/genética , Relação Estrutura-Atividade
6.
Life Sci ; 237: 116947, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31605708

RESUMO

AIMS: Pseudomonas aeruginosa is one of the leading causes of opportunistic and hospital-acquired infections worldwide, which is frequently linked with clinical treatment difficulties. Ibuprofen, a widely used non-steroidal anti-inflammatory drug, has been previously reported to exert antimicrobial activity with the specific mechanism. We hypothesized that inhibition of P. aeruginosa with ibuprofen is involved in the quorum sensing (QS) systems. MAIN METHODS: CFU was utilized to assessed the growth condition of P. aeruginosa. Crystal violent staining and acridine orange staining was used to evaluate the biofilm formation and adherence activity. The detection of QS virulence factors such as pyocyanin, elastase, protease, and rhamnolipids were applied to investigation the anti-QS activity of ibuprofen against P. aeruginosa. The production of 3-oxo-C12-HSL and C4-HSL was confirmed by liquid chromatography/mass spectrometry analysis. qRT-PCR was used to identify the QS-related gene expression. Furthermore, we explored the binding effects between ibuprofen and QS-associated proteins with molecular docking. KEY FINDINGS: Ibuprofen inhibits P. aeruginosa biofilm formation and adherence activity. And the inhibitory effects of ibuprofen on C4-HSL levels were concentration-dependent (p < 0.05), while it has no effect on 3-oxo-C12-HSL. Moreover, ibuprofen attenuates the production of virulence factors in P. aeruginosa (p < 0.05). In addition, the genes of QS system were decreased after the ibuprofen treatment (p < 0.05). Of note, ibuprofen was binding with LuxR, LasR, LasI, and RhlR at high binding scores. SIGNIFICANCE: The antibiofilm and anti-QS activity of ibuprofen suggest that it can be a candidate drug for the treatment of clinical infections with P. aeruginosa.


Assuntos
Proteínas de Bactérias/genética , Biofilmes/crescimento & desenvolvimento , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Ibuprofeno/farmacologia , Pseudomonas aeruginosa/genética , Percepção de Quorum/efeitos dos fármacos , Fatores de Virulência/genética , Anti-Inflamatórios não Esteroides/farmacologia , Biofilmes/efeitos dos fármacos , Humanos , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/crescimento & desenvolvimento
7.
Nat Commun ; 10(1): 4129, 2019 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-31511505

RESUMO

Synthetic biology and metabolic engineering have expanded the possibilities for engineered cell-based systems. The addition of non-native biosynthetic and regulatory components can, however, overburden the reprogrammed cells. In order to avoid metabolic overload, an emerging area of focus is on engineering consortia, wherein cell subpopulations work together to carry out a desired function. This strategy requires regulation of the cell populations. Here, we design a synthetic co-culture controller consisting of cell-based signal translator and growth-controller modules that, when implemented, provide for autonomous regulation of the consortia composition. The system co-opts the orthogonal autoinducer AI-1 and AI-2 cell-cell signaling mechanisms of bacterial quorum sensing (QS) to enable cross-talk between strains and a QS signal-controlled growth rate controller to modulate relative population densities. We further develop a simple mathematical model that enables cell and system design for autonomous closed-loop control of population trajectories.


Assuntos
Bactérias/crescimento & desenvolvimento , Bactérias/metabolismo , Técnicas de Cocultura/métodos , Transdução de Sinais , 4-Butirolactona/análogos & derivados , 4-Butirolactona/farmacologia , Bactérias/efeitos dos fármacos , Proteínas de Bactérias/metabolismo , Proliferação de Células/efeitos dos fármacos , Homosserina/análogos & derivados , Homosserina/farmacologia , Lactonas/farmacologia , Modelos Biológicos , Percepção de Quorum/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
8.
J Appl Microbiol ; 127(6): 1768-1775, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31487414

RESUMO

AIMS: Persister cells are stressed cells that have transient tolerance to antibiotics; these cells undergo no genetic change, but instead, their tolerance is due to reduced metabolism. Unfortunately, little is known about how persisters resuscitate, so we explored the waking of cells in the presence of the interkingdom signal indole. METHODS AND RESULTS: To generate a large population of persister cells, we induced the persister phenotype in the opportunistic pathogen Pseudomonas aeruginosa by pretreating cells with carbonyl cyanide m-chlorophenylhydrazone to reduce translation by depleting ATP levels, and found, via single cell observations, that proline is sufficient to wake the persister cells. P. aeruginosa is often present in the gastrointestinal tract, and indole from commensal bacteria such as Escherichia coli has been shown to inhibit P. aeruginosa quorum sensing and pathogenicity without influencing growth. Furthermore, indole is not toxic to P. aeruginosa persister cells. However, we find here that physiological concentrations of indole inhibit P. aeruginosa persister cell resuscitation with an efficiency of higher than 95%. Critically, when contacted with E. coli stationary-phase cultures, the indole produced by E. coli completely inhibits persister cell resuscitation of P. aeruginosa. CONCLUSIONS: Therefore, E. coli has devised a method to outcompete its competitors by preventing their resuscitation with indole. SIGNIFICANCE AND IMPACT OF THE STUDY: This work provides insight into why indole is produced by commensal bacteria.


Assuntos
Escherichia coli/metabolismo , Indóis/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Carbonil Cianeto m-Clorofenil Hidrazona/farmacologia , Técnicas de Cocultura , Indóis/metabolismo , Prolina/farmacologia , Pseudomonas aeruginosa/fisiologia , Percepção de Quorum/efeitos dos fármacos
9.
World J Microbiol Biotechnol ; 35(9): 143, 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31493142

RESUMO

Bacterial biofilms are multicellular aggregates enclosed in a self-created biopolymer matrix. Biofilm-producing bacteria have become a great public health problem worldwide because biofilms enable these microorganisms to evade several clearance mechanisms produced by host and synthetic sources. Over the past years, different flavonoids including quercetin have engrossed considerable interest among researchers owing to their potential anti-biofilm properties. To our knowledge, there is no review regarding effects of quercetin towards bacterial biofilms, prompting us to summarize experimental evidence on its anti-biofilm properties. Quercetin inhibits biofilm development by a diverse array of bacterial pathogens such as Enterococcus faecalis, Staphylococcus aureus, Streptococcus mutans, Escherichia coli, and Pseudomonas aeruginosa. Prevention of bacterial adhesion, suppression of quorum-sensing pathways, disruption or alteration of plasma membrane, inhibition of efflux pumps, and blocking nucleic acid synthesis have been documented as major anti-biofilm mechanisms of quercetin. Overall, anti-biofilm activity of quercetin can open up new horizons in a wide range of biomedical areas, from food industry to medicine.


Assuntos
Bactérias/efeitos dos fármacos , Biofilmes/efeitos dos fármacos , Quercetina/farmacologia , Aderência Bacteriana/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Membrana Celular/efeitos dos fármacos , Parede Celular/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Inibidores da Síntese de Ácido Nucleico/farmacologia , Ácidos Nucleicos/biossíntese , Percepção de Quorum/efeitos dos fármacos
10.
Eur J Pharm Sci ; 140: 105058, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31472255

RESUMO

The biofilm formation of Pseudomonas aeruginosa (P. aeruginosa) is regulated by a phenomenon of quorum sensing (QS). With 5-hydroxyl-3,4-halogenated-5H-furan-2-ones as beginning, analogs bearing alkyl chains, vinyl bromide, or aromatic rings were designed and synthesized. The minimum inhibitory concentration (MIC) of the compounds against P. aeruginosa was assayed and the biofilm inhibition ratio was determined at different concentrations lower than the MIC. C-5 aromatic substituted furanones showed remarkable biofilm formation as well as inhibition of virulence factor production in P. aeruginosa. Fluorescence report analysis identified the QS regulatory mechanism of the most active compound 29. This study provides us a novel candidate for combating drug resistant bacteria strains by merely inhibiting biofilm formation. Without suppressing the regular life cycle of the bacteria, bacterial resistance mechanisms may not be activated.


Assuntos
Furanos/química , Furanos/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Percepção de Quorum/efeitos dos fármacos , Animais , Biofilmes/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Halogenação , Camundongos , Testes de Sensibilidade Microbiana , Células RAW 264.7 , Fatores de Virulência/metabolismo
11.
Microb Pathog ; 135: 103658, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31398531

RESUMO

The increasing resistance of Pseudomonas aeruginosa towards antimicrobial agents has been a major cause for the escalation of untreatable diabetic foot ulcer cases around the globe. This demands research towards alternative natural products that inhibit biofilm formation by P. aeruginosa. The study focuses on enhancing as well as understanding the anti-biofilm property of lutein from Chlorella pyrenoidosa against MTCC strain of P. aeruginosa PAO1. C. pyrenoidosa was subjected to nutrient starvation (N-, S- and P-) and their growth, biomass, chlorophyll pigments and total carotenoids were estimated. Lutein extracted from nutrient starved C. pyrenoidosa were quantified using High Performance Liquid Chromatography (HPLC) and also used for quantification of biofilm formation, cell surface hydrophobicity (CSH), extracellular polymeric substances (EPS) and pyocyanin degradation. The results showed 20 µg/mL concentration of lutein showed maximum inhibition and degradation of biofilm formation, pyocyanin production, Cell Surface Hydrophobicity Extracellular Polymeric Substances, when compared to other concentrations. Azithromycin was used as a standard drug to compare the efficiency of lutein as a potential antibiofilm compound. Docking studies confirmed the interaction of lutein with the four proteins - LasI, LasR, RhlI and RhlR, involved in the quorum sensing mechanism during biofilm formation. Among them, RhlI protein was found to strongly interact and LasI exhibiting the least interaction with lutein. Gene expression analyses of las and rhl genes in P. aeruginosa PAO1 revealed a significant down regulation of both the genes in the cultures treated with different concentrations of lutein. Therefore, it can be understood that lutein is an effective antibiofilm agent and can be used in combination with generic drugs that are used for treating diseases such as diabetic foot ulcers, which are ineffective due to high biofilm forming capability of P. aeruginosa and other bacterial species.


Assuntos
Biofilmes/efeitos dos fármacos , Chlorella/metabolismo , Luteína/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Percepção de Quorum/efeitos dos fármacos , Azitromicina/farmacologia , Proteínas de Bactérias/genética , Biofilmes/crescimento & desenvolvimento , Biomassa , Carotenoides , Parede Celular/efeitos dos fármacos , Clorofila , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Interações Hidrofóbicas e Hidrofílicas/efeitos dos fármacos , Ligases/genética , Luteína/química , Microalgas , Simulação de Acoplamento Molecular , Pseudomonas aeruginosa/genética , Piocianina/metabolismo , Percepção de Quorum/genética , Transativadores/genética , Fatores de Transcrição/genética
12.
Microbiol Res ; 228: 126301, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31422232

RESUMO

The in vitro inhibition of quorum sensing signal, xanthan gum secretion, biofilm formation in different Xanthomonas pathovars and biological control of bacterial blight of rice by the two bioactive extrolites produced by Pseudomonas aeruginosa strain CGK-KS-1 were explored. These extrolites were extracted from Diaion HP-20 resin with methanol and purified by preparative-thin layer chromatography. Further, spectroscopic structural elucidation revealed the tentative identity of these extrolites to be (R,3E,5E,9Z,11E)-13-((3S,5R)-5-acetyl-2,6-dimethylheptan-3-yl)-10-hydroxy-4-methyl-1,8-diazabicyclo[9.3.1]pentadeca-3,5,9,11(15),13-pentaen-2-one and (R,3E,5E,8E,11E)-13-((3S,5R)-5-acetyl-2,6-dimethylheptan-3-yl)-4-methyl-1,8-diazabicyclo[9.3.1]pentadeca-3,5,8,11(15),13-pentaene-2,10-dione, named as Chumacin-1 and Chumacin-2, respectively. Antimicrobial assay showed Chumacin-1 and Chumacin-2 exhibited a strong in vitro growth inhibition against various Xanthomonas pathovars. Quorum sensing overlay assay using a reporter strain Chromobacterium violaceum strain CV026 showed that Chumacin-1 and Chumacin-2 inhibited quorum sensing signaling. The mechanistic studies revealed that these extrolites inhibited the production of quorum sensing signaling factor, cis-11-methyl-2-dodecenoic acid; suppressed the xanthan gum secretion and also inhibited the biofilms formed by various Xanthomonas pathovars. Both Chumacin-1 and Chumacin-2 showed ROS generation in the test Xanthomonas strains, resulting in in vitro cell membrane damage was revealed through CSLM and FE-SEM micrographs. Further, greenhouse experiments using Samba Mashuri (BPT-5204) revealed that seed treatment with Chumacin-1 and Chumacin-2 along with foliar spray groups showed up to ˜80% reduction in bacterial blight disease in rice. To the best of our knowledge, this is the first report on new quorum sensing inhibitors, Chumacin-1 and Chumacin-2 produced by Pseudomonas aeruginosa strain CGK-KS-1 exhibiting DSF inhibition activity in Xanthomonas oryzae pv. oryzae.


Assuntos
Agentes de Controle Biológico/isolamento & purificação , Agentes de Controle Biológico/farmacologia , Oryza/microbiologia , Doenças das Plantas/prevenção & controle , Pseudomonas aeruginosa/metabolismo , Percepção de Quorum/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Xanthomonas/efeitos dos fármacos , Anti-Infecciosos/química , Anti-Infecciosos/isolamento & purificação , Anti-Infecciosos/metabolismo , Anti-Infecciosos/farmacologia , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Agentes de Controle Biológico/química , Chromobacterium/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Doenças das Plantas/microbiologia , Polissacarídeos Bacterianos/metabolismo , Poliestirenos , Xanthomonas/metabolismo
13.
Sci Total Environ ; 696: 133869, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31450048

RESUMO

Nanoparticles are released in the environment causing a negative impact in several ecosystems such as microbial communities. To adapt to environmental changes some bacteria use a collective behaviour ruled by a cell-to-cell communication process called quorum sensing (QS). In this study, the impact of some of the most employed metal-based nanoparticles, such as zinc oxide nanoparticles (ZnONPs), titanium dioxide nanoparticles (TiO2NPs) and silver nanoparticles (AgNPs) on bacterial QS has been assessed by using two different strains of the model organism Chromobacterium violaceum and by employing different experimental conditions. TiO2NPs were tested with and without applying a previous step of UV-irradiation while the effect of AgNPs of two diameter sizes (40 and 60 nm) and two different coating agents (PVP and citrate) was evaluated. Results evidenced that all nanoparticles produced a significant effect on violacein production and therefore, in the QS system. ZnONPs mainly disrupted the QS steps related to signal perception and response whereas TiO2NPs and AgNPs affected the autoinducer biosynthesis. AgNPs with the smallest size and citrate as capping agent produced the most deleterious effect while the impact of TiO2NPs was not affected by UV irradiation. The present study provides new insights into the mechanisms by which these commonly employed metal-based nanoparticles disturb bacterial QS-based communication and clearly evidences the potential risk of releasing nanoparticles to the environment, especially for microbial communities which play a key role in many environmental and technological processes.


Assuntos
Poluentes Ambientais/toxicidade , Nanopartículas Metálicas/toxicidade , Percepção de Quorum/efeitos dos fármacos , Prata/toxicidade , Bactérias
14.
Microb Pathog ; 135: 103633, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31326562

RESUMO

Vibrio harveyi causes severe loss to the aquaculture industry due to its virulence, which is mediated by Quorum sensing (QS) and biofilm formation. In the current study, we have explored the anti-virulent properties and biofilm disruption ability of luteolin (extracted from coconut shell) and linalool against this important aquaculture pathogen. HPLC analysis of the methanolic extract of coconut shells revealed a single major peak which matched to the standard luteolin which was further elucidated by NMR studies. Further, luteolin and linalool were screened for their ability to inhibit biofilms and various quorum sensing mediated virulence factors of V. harveyi. The Minimum Inhibitory Concentration (MIC) of the two compounds was determined and the sub-inhibitory concentrations of the compounds were able to inhibit biofilm formation. Both the compounds disrupted about 60-70% mature biofilms, which was also visually observed by light microscopy. Both linalool and luteolin exhibited a significant reduction in the production of EPS and alginate in the biofilms matrix of V. harveyi which was confirmed by Scanning Electron Microscopy (SEM). Both compounds inhibited the swarming and swimming motility, the crucial quorum sensing (QS) mediated virulence of V. harveyi. The present study shows the presence of valuable polyphenolic compound like luteolin in coconut shells that are discarded as a waste. From the present study we envisage that luteolin and linalool can serve as potent anti-virulent agents to combat QS mediated infections against aquaculture pathogens.


Assuntos
Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Alimentos , Óleos Voláteis/farmacologia , Extratos Vegetais/farmacologia , Vibrio/efeitos dos fármacos , Virulência/efeitos dos fármacos , /isolamento & purificação , Alginatos/análise , Aquicultura , Sobrevivência Celular/efeitos dos fármacos , Hidroxibenzoatos/farmacologia , Luteolina/isolamento & purificação , Luteolina/farmacologia , Testes de Sensibilidade Microbiana , Percepção de Quorum/efeitos dos fármacos , Vibrio/crescimento & desenvolvimento , Vibrioses , Fatores de Virulência
15.
J Basic Microbiol ; 59(9): 936-949, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31347191

RESUMO

Vibrio harveyi is a marine luminous pathogen, which causes biofilm-mediated infections, pressures the search for an innovative alternate approach to strive against vibriosis in aquaculture. This study anticipated to explore the effect of glycolipid biosurfactant as an antipathogenic against V. harveyi to control vibriosis. In this study, 27 bacterial strains were isolated from marine soil sediments. Out of these, 11 strains exhibited surfactant activity and the strain MK3 showed high emulsification index. The potent strain was identified as Vibrio natriegens and named as V. natriegens MK3. The extracted biosurfactant was purified using high-performance liquid chromatography and it was efficient to decrease the surface tension of the growth medium up to 21 mN/m. The functional group and composition of the biosurfactant were determined by Fourier-transform infrared spectroscopy and nuclear magnetic resonance spectroscopy spectral studies and the nature of the biosurfactant was identified as glycolipid. The surfactant was capable of reducing the biofilm formation, bioluminescence, extracellular polysaccharide synthesis, and quorum sensing in marine shrimp pathogen V. harveyi. The antagonistic effect of biosurfactant was evaluated against V. harveyi-infected brine shrimp Artemia salina. This study reveals that biosurfactant can be considered for the management of biofilm-related aquatic infections.


Assuntos
Biofilmes/efeitos dos fármacos , Tensoativos/farmacologia , Vibrio/química , Vibrio/efeitos dos fármacos , Virulência/efeitos dos fármacos , Animais , Aquicultura , Artemia/microbiologia , Biofilmes/crescimento & desenvolvimento , Poluição por Petróleo , Percepção de Quorum/efeitos dos fármacos , Tensoativos/isolamento & purificação , Vibrio/crescimento & desenvolvimento , Vibrio/patogenicidade , Vibrioses/prevenção & controle , Vibrioses/veterinária
16.
BMC Complement Altern Med ; 19(1): 177, 2019 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-31319827

RESUMO

BACKGROUND: Quercus gall extracts' ability to kill pathogens in vitro and even removal of chronic drug-resistant infections has been reported by several studies. The current investigation is focused on the action of extracts of Quercus infectoria gall in their sub-inhibitory concentrations on the corresponding bacterial behaviours instead of killing them. METHODS: The effect of gall extracts on the quorum sensing (QS) associated virulence of multiple drug resistant Pseudomonas aeruginosa recovered from burns wounds was studied. The influence of different extracts on the production of bacterial virulence and biofilm, and expression of the genes encoding quorum sensing and exotoxin A were investigated. Quorum sensing is a crucial regulator of virulence and biofilm development in Pseudomonas aeruginosa and other medical related microbes. RESULTS: Experiments to characterise and quantify Q. infectoria gall extracts impact on the quorum sensing networks of P.aeruginosa revealed that the expression of las, rhl, and exotoxin A (ETA) genes levels including the associated virulence were reduced by the extracts at their subinhibitory concentrations. CONCLUSIONS: The obtained results indicated that extracts of Q. infectoria galls fight infections either by their inhibitory constituents, which vigorously eradicate cells or by disruption of the pathogens quorum sensing system through weakening the virulence and bacterial coordination.


Assuntos
Proteínas de Bactérias/metabolismo , Biofilmes/efeitos dos fármacos , Extratos Vegetais/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/fisiologia , Quercus/química , Percepção de Quorum/efeitos dos fármacos , Fatores de Virulência/metabolismo , Proteínas de Bactérias/genética , Tumores de Planta , Pseudomonas aeruginosa/genética , Fatores de Virulência/genética
17.
Mar Drugs ; 17(7)2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31266202

RESUMO

Quorum sensing (QS) antagonists have been proposed as novel therapeutic agents to combat bacterial infections. We previously reported that the secondary metabolite 3-methyl-N-(2'-phenylethyl)-butyramide, produced by a marine bacterium identified as Halobacillus salinus, inhibits QS controlled phenotypes in multiple Gram-negative reporter strains. Here we report that N-phenethyl hexanamide, a structurally-related compound produced by the marine bacterium Vibrio neptunius, similarly demonstrates QS inhibitory properties. To more fully explore structure-activity relationships within this new class of QS inhibitors, a panel of twenty analogs was synthesized and biologically evaluated. Several compounds were identified with increased attenuation of QS-regulated phenotypes, most notably N-(4-fluorophenyl)-3-phenylpropanamide against the marine pathogen Vibrio harveyi (IC50 = 1.1 µM). These findings support the opportunity to further develop substituted phenethylamides as QS inhibitors.


Assuntos
Amidas/farmacologia , Antibacterianos/farmacologia , Halobacillus/metabolismo , Percepção de Quorum/efeitos dos fármacos , Amidas/química , Amidas/metabolismo , Antibacterianos/química , Antibacterianos/metabolismo , Concentração Inibidora 50 , Metabolismo Secundário , Relação Estrutura-Atividade , Vibrio/efeitos dos fármacos , Vibrio/fisiologia
18.
Microbiol Res ; 226: 19-26, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31284940

RESUMO

Pseudomonas aeruginosa is one of the most common pathogens associated with nosocomial infections and a great concern to immunocompromised individuals especially in the cases of cystic fibrosis, AIDS and burn wounds. The pathogenicity of P. aeruginosa is largely directed by the quorum sensing (QS) system. Hence, QS may be considered an important therapeutic target to combat P. aeruginosa infections. The anti-quorum sensing and anti-biofilm efficacy of aromatic aldehyde, 5-hydroxymethylfurfural (5-HMF) against P. aeruginosa PAO1 were assessed. At the sub-inhibitory concentration, 5-HMF suppressed the production of QS-controlled virulence phenotypes and biofilm formation in P. aeruginosa. It was also able to significantly enhance the survival rate of C. elegans infected with P. aeruginosa. The in silico studies revealed that 5-HMF could serve as a competitive inhibitor for the auto-inducer molecules as it exhibited a strong affinity for the regulatory proteins of the QS-circuits i.e. LasR and RhlR. In addition, a significant down-regulation in the expression of QS-related genes was observed suggesting the ability of 5-HMF in mitigating the pathogenicity of P. aeruginosa.


Assuntos
Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Furaldeído/análogos & derivados , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/patogenicidade , Percepção de Quorum/efeitos dos fármacos , Animais , Proteínas de Bactérias , Caenorhabditis elegans , Simulação por Computador , Modelos Animais de Doenças , Furaldeído/farmacologia , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Percepção de Quorum/genética , Taxa de Sobrevida , Transativadores , Virulência/efeitos dos fármacos , Fatores de Virulência
19.
Mar Drugs ; 17(7)2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-31261836

RESUMO

N-Acylhomoserine lactonase degrades the lactone ring of N-acylhomoserine lactones (AHLs) and has been widely suggested as a promising candidate for use in bacterial disease control. While a number of AHL lactonases have been characterized, none of them has been developed as a commercially available enzymatic product for in vitro AHL quenching due to their low stability. In this study, a highly stable AHL lactonase (AhlX) was identified and isolated from the marine bacterium Salinicola salaria MCCC1A01339. AhlX is encoded by a 768-bp gene and has a predicted molecular mass of 29 kDa. The enzyme retained approximately 97% activity after incubating at 25 °C for 12 days and ~100% activity after incubating at 60 °C for 2 h. Furthermore, AhlX exhibited a high salt tolerance, retaining approximately 60% of its activity observed in the presence of 25% NaCl. In addition, an AhlX powder made by an industrial spray-drying process attenuated Erwinia carotovora infection. These results suggest that AhlX has great potential for use as an in vitro preventive and therapeutic agent for bacterial diseases.


Assuntos
Antibacterianos/farmacologia , Organismos Aquáticos/enzimologia , Proteínas de Bactérias/farmacologia , Hidrolases de Éster Carboxílico/farmacologia , Halomonadaceae/enzimologia , Acil-Butirolactonas/química , Antibacterianos/química , Antibacterianos/isolamento & purificação , Proteínas de Bactérias/química , Proteínas de Bactérias/isolamento & purificação , Biotecnologia , Brassica rapa/microbiologia , Hidrolases de Éster Carboxílico/química , Hidrolases de Éster Carboxílico/isolamento & purificação , Ensaios Enzimáticos , Estabilidade Enzimática , Pectobacterium carotovorum/efeitos dos fármacos , Pectobacterium carotovorum/fisiologia , Doenças das Plantas/microbiologia , Doenças das Plantas/prevenção & controle , Percepção de Quorum/efeitos dos fármacos , Solanum tuberosum/microbiologia , Temperatura Ambiente
20.
Mar Drugs ; 17(7)2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31340463

RESUMO

Antibiotic resistance has been increasingly reported for a wide variety of bacteria of clinical significance. This widespread problem constitutes one of the greatest challenges of the twenty-first century. Faced with this issue, clinicians and researchers have been persuaded to design novel strategies in order to try to control pathogenic bacteria. Therefore, the discovery and elucidation of the mechanisms underlying bacterial pathogenesis and intercellular communication have opened new perspectives for the development of alternative approaches. Antipathogenic and/or antivirulence therapies based on the interruption of quorum sensing pathways are one of several such promising strategies aimed at disarming rather than at eradicating bacterial pathogens during the course of colonization and infection. This review describes mechanisms of bacterial communication involved in biofilm formation. An overview of the potential of marine bacteria and their bioactive components as QS inhibitors is further provided.


Assuntos
Antibacterianos/farmacologia , Organismos Aquáticos/imunologia , Infecções Bacterianas/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Percepção de Quorum/efeitos dos fármacos , Antibacterianos/uso terapêutico , Organismos Aquáticos/metabolismo , Bactérias/efeitos dos fármacos , Bactérias/patogenicidade , Infecções Bacterianas/microbiologia , Biofilmes/efeitos dos fármacos , Produtos Biológicos/imunologia , Produtos Biológicos/metabolismo , Resistência Microbiana a Medicamentos/efeitos dos fármacos , Humanos
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