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1.
Front Cell Infect Microbiol ; 14: 1413728, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39015339

RESUMO

Pseudomonas aeruginosa has already been stipulated as a "critical" pathogen, emphasizing the urgent need for researching and developing novel antibacterial agents due to multidrug resistance. Bacterial biofilm formation facilitates cystic fibrosis development and restricts the antibacterial potential of many current antibiotics. The capacity of P. aeruginosa to form biofilms and resist antibiotics is closely correlated with quorum sensing (QS). Bacterial QS is being contemplated as a promising target for developing novel antibacterial agents. QS inhibitors are a promising strategy for treating chronic infections. This study reported that the active compound PT22 (1H-pyrrole-2,5-dicarboxylic acid) isolated from Perenniporia tephropora FF2, one endophytic fungus from Areca catechu L., presents QS inhibitory activity against P. aeruginosa. Combined with gentamycin or piperacillin, PT22 functions as a novel antibiotic accelerant against P. aeruginosa. PT22 (0.50 mg/mL, 0.75 mg/mL, and 1.00 mg/mL) reduces the production of QS-related virulence factors, such as pyocyanin and rhamnolipid, and inhibits biofilm formation of P. aeruginosa PAO1 instead of affecting its growth. The architectural disruption of the biofilms was confirmed by visualization through scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). Real-time quantitative PCR (RT-qPCR) indicated that PT22 significantly attenuated the expression of QS-related genes followed by docking analysis of molecules against QS activator proteins. PT22 dramatically increased the survival rate of Galleria mellonella. PT22 combined with gentamycin or piperacillin presents significant inhibition of biofilm formation and eradication of mature biofilm compared to monotherapy, which was also confirmed by visualization through SEM and CLSM. After being treated with PT22 combined with gentamycin or piperacillin, the survival rates of G. mellonella were significantly increased compared to those of monotherapy. PT22 significantly enhanced the susceptibility of gentamycin and piperacillin against P. aeruginosa PAO1. Our results suggest that PT22 from P. tephropora FF2 as a potent QS inhibitor is a candidate antibiotic accelerant to combat the antibiotic resistance of P. aeruginosa.


Assuntos
Antibacterianos , Biofilmes , Pseudomonas aeruginosa , Pirróis , Percepção de Quorum , Pseudomonas aeruginosa/efeitos dos fármacos , Percepção de Quorum/efeitos dos fármacos , Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Pirróis/farmacologia , Animais , Fatores de Virulência/genética , Endófitos/química , Endófitos/metabolismo , Testes de Sensibilidade Microbiana , Ácidos Dicarboxílicos/farmacologia , Simulação de Acoplamento Molecular , Piocianina/metabolismo
2.
World J Microbiol Biotechnol ; 40(9): 265, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38990361

RESUMO

The increasing prevalence of infections related to methicillin-resistant Staphylococcus aureus (MRSA) necessitates the exploration of innovative therapeutic strategies that diverge from conventional antibiotic treatments. This is imperative to effectively combat resistance and manage these infections. The adoption of antivirulence strategies has emerged as a particularly promising avenue. This approach applies a heightened selective pressure on pathogens, thereby diminishing the likelihood of bacteria evolving resistance to antibiotics. In our pursuit of novel therapeutics for treating MRSA infections, we have focused on agents that inhibit the virulence of S. aureus without impeding its growth, aiming to minimize the development of drug resistance. α-Hemolysin, a critical virulence factor encoded by the hla gene, is a cytotoxin that forms pores in host cell membranes and plays a pivotal role in the progression of disease during bacterial infections. Herein, we identified that norwogonin could effectively inhibit Hla production via targeting agrAC, a crucial protein in quorum sensing, resulting in dose-dependent inhibition of hemolytic activity without suppressing S. aureus growth. In vitro assays illustrated that norwogonin decreased the thermal stability of agrAC, providing evidence of interaction between norwogonin and agrAC. Meanwhile, norwogonin alleviated Hla-mediated A549 cell damage and reduced lactate dehydrogenase release. In vivo studies suggested that norwogonin treatment blocked the establishment of a mouse model of pneumonia caused by S. aureus USA300. Notably, norwogonin enhanced the antibacterial potency of oxacillin. In conclusion, norwogonin is a promising candidate for treating S. aureus infections, offering a novel alternative to traditional antibiotics by targeting virulence factors and enhancing the efficacy of existing treatments.


Assuntos
Antibacterianos , Proteínas de Bactérias , Proteínas Hemolisinas , Staphylococcus aureus Resistente à Meticilina , Fatores de Virulência , Animais , Feminino , Humanos , Camundongos , Células A549 , Antibacterianos/farmacologia , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Toxinas Bacterianas/metabolismo , Modelos Animais de Doenças , Proteínas Hemolisinas/metabolismo , Hemólise/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Percepção de Quorum/efeitos dos fármacos , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Virulência/efeitos dos fármacos , Fatores de Virulência/metabolismo
3.
Nat Commun ; 15(1): 5625, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38987237

RESUMO

Competence for natural transformation is a central driver of genetic diversity in bacteria. In the human pathogen Streptococcus pneumoniae, competence exhibits a populational character mediated by the stress-induced ComABCDE quorum-sensing (QS) system. Here, we explore how this cell-to-cell communication mechanism proceeds and the functional properties acquired by competent cells grown under lethal stress. We show that populational competence development depends on self-induced cells stochastically emerging in response to stresses, including antibiotics. Competence then propagates through the population from a low threshold density of self-induced cells, defining a biphasic Self-Induction and Propagation (SI&P) QS mechanism. We also reveal that a competent population displays either increased sensitivity or improved tolerance to lethal doses of antibiotics, dependent in the latter case on the competence-induced ComM division inhibitor. Remarkably, these surviving competent cells also display an altered transformation potential. Thus, the unveiled SI&P QS mechanism shapes pneumococcal competence as a health sensor of the clonal population, promoting a bet-hedging strategy that both responds to and drives cells towards heterogeneity.


Assuntos
Antibacterianos , Proteínas de Bactérias , Percepção de Quorum , Streptococcus pneumoniae , Streptococcus pneumoniae/efeitos dos fármacos , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/fisiologia , Antibacterianos/farmacologia , Percepção de Quorum/efeitos dos fármacos , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Humanos , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Transformação Bacteriana
4.
Med Microbiol Immunol ; 213(1): 16, 2024 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-39033094

RESUMO

Melioidosis is a severe infectious disease caused by Burkholderia pseudomallei, an intracellular pathogen with a high mortality rate and significant antibiotic resistance. The high mortality rate and resistance to antibiotics have drawn considerable attention from researchers studying melioidosis. This study evaluated the effects of various concentrations (75, 50, and 25 µg/mL) of promethazine hydrochloride (PTZ), a potent antihistamine, on biofilm formation and lipase activity after 24 h of exposure to B. thailandensis E264. A concentration-dependent decrease in both biofilm biomass and lipase activity was observed. RT-PCR analysis revealed that PTZ treatment not only made the biofilm structure loose but also reduced the expression of btaR1, btaR2, btaR3, and scmR. Single gene knockouts of quorum sensing (QS) receptor proteins (∆btaR1, ∆btaR2, and ∆btaR3) were successfully constructed. Deletion of btaR1 affected biofilm formation in B. thailandensis, while deletion of btaR2 and btaR3 led to reduced lipase activity. Molecular docking and biological performance results demonstrated that PTZ inhibits biofilm formation and lipase activity by suppressing the expression of QS-regulated genes. This study found that repositioning PTZ reduced biofilm formation in B. thailandensis E264, suggesting a potential new approach for combating melioidosis.


Assuntos
Biofilmes , Burkholderia , Reposicionamento de Medicamentos , Prometazina , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Burkholderia/efeitos dos fármacos , Burkholderia/fisiologia , Burkholderia/genética , Prometazina/farmacologia , Simulação de Acoplamento Molecular , Antibacterianos/farmacologia , Lipase/metabolismo , Lipase/genética , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Humanos , Percepção de Quorum/efeitos dos fármacos
5.
Nat Commun ; 15(1): 5746, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38982056

RESUMO

Candida albicans and Staphylococcus aureus are two commonly associated pathogens that cause nosocomial infections with high morbidity and mortality. Our prior and current work using a murine model of polymicrobial intra-abdominal infection (IAI) demonstrates that synergistic lethality is driven by Candida-induced upregulation of functional S. aureus α-toxin leading to polymicrobial sepsis and organ damage. In order to determine the candidal effector(s) mediating enhanced virulence, an unbiased screen of C. albicans transcription factor mutants was undertaken revealing that zcf13Δ/Δ fails to drive augmented α-toxin or lethal synergism during co-infection. A combination of transcriptional and phenotypic profiling approaches shows that ZCF13 regulates genes involved in pentose metabolism, including RBK1 and HGT7 that contribute to fungal ribose catabolism and uptake, respectively. Subsequent experiments reveal that ribose inhibits the staphylococcal agr quorum sensing system and concomitantly represses toxicity. Unlike wild-type C. albicans, zcf13Δ/Δ did not effectively utilize ribose during co-culture or co-infection leading to exogenous ribose accumulation and agr repression. Forced expression of RBK1 and HGT7 in the zcf13Δ/Δ mutant fully restores pathogenicity during co-infection. Collectively, our results detail the interwoven complexities of cross-kingdom interactions and highlight how intermicrobial metabolism impacts polymicrobial disease pathogenesis with devastating consequences for the host.


Assuntos
Candida albicans , Candidíase , Coinfecção , Proteínas Fúngicas , Infecções Estafilocócicas , Staphylococcus aureus , Candida albicans/metabolismo , Candida albicans/patogenicidade , Candida albicans/genética , Animais , Coinfecção/microbiologia , Staphylococcus aureus/patogenicidade , Staphylococcus aureus/metabolismo , Staphylococcus aureus/genética , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/metabolismo , Candidíase/microbiologia , Camundongos , Proteínas Fúngicas/metabolismo , Proteínas Fúngicas/genética , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Infecções Intra-Abdominais/microbiologia , Feminino , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Percepção de Quorum/genética , Virulência , Regulação Fúngica da Expressão Gênica , Modelos Animais de Doenças , Transativadores/metabolismo , Transativadores/genética
6.
Microb Pathog ; 193: 106787, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38992510

RESUMO

A unique approach is imperative for the development of drugs aimed at inhibiting various stages of infection, rather than solely focusing on bacterial viability. Among the array of unconventional targets explored for formulating novel antimicrobial medications, blocking the quorum-sensing (QS) system emerges as a highly effective and promising strategy against a variety of pathogenic microbes. In this investigation, we have successfully assessed nine α-aminoamides for their anti-QS activity using Agrobacterium tumefaciensNT1 as a biosensor strain. Among these compounds, three (2, 3and, 4) have been identified as potential anti-QS candidates. Molecular docking studies have further reinforced these findings, indicating that these compounds exhibit favorable pharmacokinetic profiles. Additionally, we have assessed the ligand's stability within the protein's binding pocket using molecular dynamics (MD) simulations and MMGBSA analysis. Further, combination of antiquorum sensing properties with antibiotics viaself-assembly represents a promising approach to enhance antibacterial efficacy, overcome resistance, and mitigate the virulence of bacterial pathogens. The release study also reflects a slow and gradual release of the metronidazole at both pH 6.5 and pH 7.4, avoiding the peaks and troughs associated with more immediate release formulations.


Assuntos
Agrobacterium tumefaciens , Antibacterianos , Metronidazol , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Percepção de Quorum , Agrobacterium tumefaciens/efeitos dos fármacos , Percepção de Quorum/efeitos dos fármacos , Metronidazol/farmacologia , Metronidazol/química , Antibacterianos/farmacologia , Antibacterianos/química , Testes de Sensibilidade Microbiana , Géis/química , Sinergismo Farmacológico , Liberação Controlada de Fármacos
7.
Sci Rep ; 14(1): 15666, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38977845

RESUMO

Inter-cellular signaling, referred to as quorum sensing (QS), regulates the production of virulence factors in numerous gram-negative bacteria, such as the human pathogens Pseudomonas aeruginosa and Chromobacterium violaceum. QS inhibition may provide an opportunity for the treatment of bacterial infections. This represents the initial study to examine the antibiofilm and antivirulence capabilities of rose absolute and its primary component, phenylethyl alcohol. QS inhibition was assessed by examining extracellular exopolysaccharide synthesis, biofilm development, and swarming motility in P. aeruginosa PAO1, along with violacein production in C. violaceum ATCC 12472. Molecular docking analysis was conducted to explore the mechanism by which PEA inhibits QS. Our results indicate that rose absolute and PEA caused decrease in EPS production (60.5-33.5%), swarming motility (94.7-64.5%), and biofilm formation (98.53-55.5%) in the human pathogen P. aeruginosa PAO1. Violacein production decreased by 98.1% and 62.5% with an absolute (0.5 v/v %) and PEA (2 mM). Moreover, the molecular docking analysis revealed a promising competitive interaction between PEA and AHLs. Consequently, this study offers valuable insights into the potential of rose absolute and PEA as inhibitors of QS in P. aeruginosa and C. violaceum.


Assuntos
Biofilmes , Chromobacterium , Simulação de Acoplamento Molecular , Álcool Feniletílico , Pseudomonas aeruginosa , Percepção de Quorum , Percepção de Quorum/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/fisiologia , Chromobacterium/efeitos dos fármacos , Chromobacterium/fisiologia , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Álcool Feniletílico/farmacologia , Álcool Feniletílico/análogos & derivados , Álcool Feniletílico/química , Álcool Feniletílico/metabolismo , Antibacterianos/farmacologia , Antibacterianos/química , Indóis/farmacologia , Indóis/metabolismo
8.
Int J Mol Sci ; 25(13)2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-39000246

RESUMO

Quorum sensing (QS) allows bacteria to coordinate their activities by producing and detecting low-molecular-weight signal molecules based on population density, thereby controlling the infectivity of bacteria through various virulence factors. Quorum-sensing inhibition is a promising approach to tackle bacterial communication. Cyclodextrins (CDs) are a class of cyclic oligosaccharides that reversibly encapsulate the acyl chain of the signal molecules, thereby preventing their binding to receptors and interrupting bacterial communication. This results in the inhibition of the expression of various properties, including different virulence factors. To examine the potential quorum-quenching (QQ) ability of newly prepared cyclodextrin derivatives, we conducted short-term tests using Aliivibrio fischeri, a heterotrophic marine bacterium capable of bioluminescence controlled by quorum sensing. α- and ß-cyclodextrins monosubstituted with alkylthio moieties and further derivatized with quaternary ammonium groups were used as the test agents. The effect of these cyclodextrins on the quorum-sensing system of A. fischeri was investigated by adding them to an exponential growth phase of the culture and then measuring bioluminescence intensity, population growth, and cell viability. Our results demonstrate that the tested cyclodextrins have an inhibitory effect on the quorum-sensing system of A. fischeri. The inhibitory effect varies based on the length of the alkyl chain, with alkylthio substitution enhancing it and the presence of quaternary ammonium groups decreasing it. Our findings suggest that cyclodextrins can be a promising therapeutic agent for the treatment of bacterial infections.


Assuntos
Aliivibrio fischeri , Ciclodextrinas , Percepção de Quorum , Aliivibrio fischeri/efeitos dos fármacos , Percepção de Quorum/efeitos dos fármacos , Ciclodextrinas/farmacologia , Ciclodextrinas/química , Medições Luminescentes/métodos , Luminescência
9.
Appl Microbiol Biotechnol ; 108(1): 418, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39012538

RESUMO

Pseudomonas aeruginosa (P. aeruginosa) biofilm formation is a crucial cause of enhanced antibiotic resistance. Quorum sensing (QS) is involved in regulating biofilm formation; QS inhibitors block the QS signaling pathway as a new strategy to address bacterial resistance. This study investigated the potential and mechanism of L-HSL (N-(3-cyclic butyrolactone)-4-trifluorophenylacetamide) as a QS inhibitor for P. aeruginosa. The results showed that L-HSL effectively inhibited the biofilm formation and dispersed the pre-formed biofilm of P. aeruginosa. The production of extracellular polysaccharides and the motility ability of P. aeruginosa were suppressed by L-HSL. C. elegans infection experiment showed that L-HSL was non-toxic and provided protection to C. elegans against P. aeruginosa infection. Transcriptomic analysis revealed that L-HSL downregulated genes related to QS pathways and biofilm formation. L-HSL exhibits a promising potential as a therapeutic drug for P. aeruginosa infection. KEY POINTS: • Chemical synthesis of N-(3-cyclic butyrolactone)-4-trifluorophenylacetamide, named L-HSL. • L-HSL does not generate survival pressure on the growth of P. aeruginosa and can inhibit the QS system. • KEGG enrichment analysis found that after L-HSL treatment, QS-related genes were downregulated.


Assuntos
4-Butirolactona , Biofilmes , Caenorhabditis elegans , Pseudomonas aeruginosa , Percepção de Quorum , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/fisiologia , Pseudomonas aeruginosa/genética , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Percepção de Quorum/efeitos dos fármacos , Caenorhabditis elegans/efeitos dos fármacos , Caenorhabditis elegans/microbiologia , Animais , 4-Butirolactona/análogos & derivados , 4-Butirolactona/farmacologia , 4-Butirolactona/metabolismo , Antibacterianos/farmacologia , Perfilação da Expressão Gênica , Homosserina/análogos & derivados , Homosserina/metabolismo , Homosserina/farmacologia , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos
10.
Sci Rep ; 14(1): 16181, 2024 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-39003361

RESUMO

Quorum sensing (QS) is a communication form between bacteria via small signal molecules that enables global gene regulation as a function of cell density. We applied a microfluidic mother machine to study the kinetics of the QS response of Pseudomonas aeruginosa bacteria to additions and withdrawals of signal molecules. We traced the fast buildup and the subsequent considerably slower decay of a population-level and single-cell-level QS response. We applied a mathematical model to explain the results quantitatively. We found significant heterogeneity in QS on the single-cell level, which may result from variations in quorum-controlled gene expression and protein degradation. Heterogeneity correlates with cell lineage history, too. We used single-cell data to define and quantitatively characterize the population-level quorum state. We found that the population-level QS response is well-defined. The buildup of the quorum is fast upon signal molecule addition. At the same time, its decay is much slower following signal withdrawal, and the quorum may be maintained for several hours in the absence of the signal. Furthermore, the quorum sensing response of the population was largely repeatable in subsequent pulses of signal molecules.


Assuntos
Proteínas de Bactérias , Pseudomonas aeruginosa , Percepção de Quorum , Análise de Célula Única , Transativadores , Pseudomonas aeruginosa/fisiologia , Pseudomonas aeruginosa/metabolismo , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Transativadores/metabolismo , Transativadores/genética , Regulação Bacteriana da Expressão Gênica , Transdução de Sinais , Cinética
11.
PLoS Comput Biol ; 20(7): e1011696, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38976753

RESUMO

Quorum sensing (QS) is a regulatory mechanism used by bacteria to coordinate group behavior in response to high cell densities. During QS, cells monitor the concentration of external signals, known as autoinducers, as a proxy for cell density. QS often involves positive feedback loops, leading to the upregulation of genes associated with QS signal production and detection. This results in distinct steady-state concentrations of QS-related molecules in QS-ON and QS-OFF states. Due to the slow decay rates of biomolecules such as proteins, even after removal of the initial stimuli, cells can retain elevated levels of QS-associated biomolecules for extended periods of time. This persistence of biomolecules after the removal of the initial stimuli has the potential to impact the response to future stimuli, indicating a memory of past exposure. This phenomenon, which is a consequence of the carry-over of biomolecules rather than genetic inheritance, is known as "phenotypic" memory. This theoretical study aims to investigate the presence of phenotypic memory in QS and the conditions that influence this memory. Numerical simulations based on ordinary differential equations and analytical modeling were used to study gene expression in response to sudden changes in cell density and extracellular signal concentrations. The model examined the effect of various cellular parameters on the strength of QS memory and the impact on gene regulatory dynamics. The findings revealed that QS memory has a transient effect on the expression of QS-responsive genes. These consequences of QS memory depend strongly on how cell density was perturbed, as well as various cellular parameters, including the Fold Change in the expression of QS-regulated genes, the autoinducer synthesis rate, the autoinducer threshold required for activation, and the cell growth rate.


Assuntos
Percepção de Quorum , Percepção de Quorum/fisiologia , Percepção de Quorum/genética , Fenótipo , Modelos Biológicos , Biologia Computacional , Regulação Bacteriana da Expressão Gênica , Simulação por Computador , Fenômenos Fisiológicos Bacterianos
12.
Food Microbiol ; 122: 104535, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38839215

RESUMO

A promising strategy to control bacterial diseases involves using Quorum Sensing Inhibitor (QSI) compounds. This study aimed to evaluate the potential of Falcaria vulgaris plant extract to combat the phytopathogenic Pectobacterium carotovorum subsp. carotovorum (Pcc) via its QSI activity. Using biosensors and Minimum Inhibitory Concentration (MIC) assays, the QSI and antimicrobial aspects of the extract were assessed. Furthermore, the effect of the extract on the reduction of tuber maceration in potatoes was examined. Subsequently, homology modeling based on LasR was conducted to analyze interactions between ligand 3-oxo-C8-AHL, and ExpR2 protein. Docking studies were performed on all extract compounds identified via Gas Chromatography-Mass Spectrometry (GC-MS) analysis. The extract effectively reduced maceration at sub-MIC concentrations across various pathogenic strains. Furthermore, Cyclopentadecanone, 2-hydroxy, showed more negative docking energy than the native ligand. Z,E-2,13-Octadecadien-1-ol showed energy equivalence to the native ligand. Additionally, this plant included certain compounds or their analogs that had previously been discovered as QSI compounds. These compounds included oleic acid, n-Hexadecanoic acid, cytidine, and linoleic acid, and they had energies that were comparable to that of the native ligand. In conclusion, the remarkable QSI property showed by this plant is likely attributed to a combination of compounds possessing this characteristic.


Assuntos
Antibacterianos , Simulação de Acoplamento Molecular , Pectobacterium carotovorum , Extratos Vegetais , Percepção de Quorum , Percepção de Quorum/efeitos dos fármacos , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Pectobacterium carotovorum/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/química , Testes de Sensibilidade Microbiana , Solanum tuberosum/microbiologia , Solanum tuberosum/química , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Doenças das Plantas/microbiologia , Doenças das Plantas/prevenção & controle
13.
Lett Appl Microbiol ; 77(7)2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38886121

RESUMO

Hafnia sp. was one of the specific spoilage bacteria in aquatic products, and the aim of the study was to investigate the inhibition ability of the silver nanoparticles (AgNPs) biosynthesis by an aqueous extract of Prunus persica leaves toward the spoilage-related virulence factors of Hafnia sp. The synthesized P-AgNPs were spherical, with a mean particle size of 36.3 nm and zeta potential of 21.8 ± 1.33 mV. In addition, the inhibition effects of P-AgNPs on the growth of two Hafnia sp. strains and their quorum sensing regulated virulence factors, such as the formation of biofilm, secretion of N-acetyl-homoserine lactone (AHLs), proteases, and exopolysaccharides, as well as their swarming and swimming motilities were evaluated. P-AgNPs had a minimum inhibitory concentration (MIC) of 64 µg ml-1 against the two Hafnia sp. strains. When the concentration of P-AgNPs was below MIC, it could inhibit the formation of biofilms by Hafnia sp at 8-32 µg ml-1, but it promoted the formation of biofilms by Hafnia sp at 0.5-4 µg ml-1. P-AgNPs exhibited diverse inhibiting effects on AHLs and protease production, swimming, and swarming motilities at various concentrations.


Assuntos
Antibacterianos , Biofilmes , Nanopartículas Metálicas , Testes de Sensibilidade Microbiana , Extratos Vegetais , Folhas de Planta , Prunus persica , Percepção de Quorum , Prata , Percepção de Quorum/efeitos dos fármacos , Prata/farmacologia , Prata/química , Prata/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Folhas de Planta/microbiologia , Folhas de Planta/química , Nanopartículas Metálicas/química , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Antibacterianos/farmacologia , Prunus persica/microbiologia , Aizoaceae/química , Fatores de Virulência/metabolismo
14.
Vet Res ; 55(1): 80, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38886823

RESUMO

Bacteria utilize intercellular communication to orchestrate essential cellular processes, adapt to environmental changes, develop antibiotic tolerance, and enhance virulence. This communication, known as quorum sensing (QS), is mediated by the exchange of small signalling molecules called autoinducers. AI-2 QS, regulated by the metabolic enzyme LuxS (S-ribosylhomocysteine lyase), acts as a universal intercellular communication mechanism across gram-positive and gram-negative bacteria and is crucial for diverse bacterial processes. In this study, we demonstrated that in Streptococcus suis (S. suis), a notable zoonotic pathogen, AI-2 QS enhances galactose utilization, upregulates the Leloir pathway for capsular polysaccharide (CPS) precursor production, and boosts CPS synthesis, leading to increased resistance to macrophage phagocytosis. Additionally, our molecular docking and dynamics simulations suggest that, similar to S. pneumoniae, FruA, a fructose-specific phosphoenolpyruvate phosphotransferase system prevalent in gram-positive pathogens, may also function as an AI-2 membrane surface receptor in S. suis. In conclusion, our study demonstrated the significance of AI-2 in the synthesis of galactose metabolism-dependent CPS in S. suis. Additionally, we conducted a preliminary analysis of the potential role of FruA as a membrane surface receptor for S. suis AI-2.


Assuntos
Galactose , Percepção de Quorum , Streptococcus suis , Streptococcus suis/fisiologia , Galactose/metabolismo , Percepção de Quorum/fisiologia , Virulência , Animais , Cápsulas Bacterianas/metabolismo , Lactonas/metabolismo , Infecções Estreptocócicas/veterinária , Infecções Estreptocócicas/microbiologia , Infecções Estreptocócicas/imunologia , Homosserina/análogos & derivados , Homosserina/metabolismo , Polissacarídeos Bacterianos/metabolismo
15.
Microb Pathog ; 193: 106730, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38851361

RESUMO

Pseudomonas aeruginosa is an opportunistic pathogen that poses a significant threat to individuals suffering from cystic fibrosis (CF). The pathogen is highly prevalent in CF individuals and is responsible for chronic infection, resulting in severe tissue damage and poor patient outcome. Prolonged antibiotic administration has led to the emergence of multidrug resistance in P. aeruginosa. In this direction, antivirulence strategies achieving targeted inhibition of bacterial virulence pathways, including quorum sensing, efflux pumps, lectins, and iron chelators, have been explored against CF isolates of P. aeruginosa. Hence, this review article presents a bird's eye view on the pulmonary infections involving P. aeruginosa in CF patients by laying emphasis on factors contributing to bacterial colonization, persistence, and disease progression along with the current line of therapeutics against P. aeruginosa in CF. We further collate scientific literature and discusses various antivirulence strategies that have been tested against P. aeruginosa isolates from CF patients.


Assuntos
Antibacterianos , Fibrose Cística , Infecções por Pseudomonas , Pseudomonas aeruginosa , Percepção de Quorum , Fibrose Cística/microbiologia , Fibrose Cística/complicações , Fibrose Cística/tratamento farmacológico , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/patogenicidade , Humanos , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/microbiologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Percepção de Quorum/efeitos dos fármacos , Virulência/efeitos dos fármacos , Fatores de Virulência , Farmacorresistência Bacteriana Múltipla , Animais
16.
Microb Pathog ; 193: 106739, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38857709

RESUMO

Enterococcus faecalis, an opportunistic pathogen responsible for nosocomial infections, exhibits increased pathogenicity via biofilm formation. Theaflavin-3,3'-digallate (TF3), a theaflavin extracted from black tea, exhibits potent antibacterial effects. In the present study, we investigated the inhibitory effect of TF3 on E. faecalis. Our results indicated that TF3 significantly inhibited E. faecalis ATCC 29212 biofilm formation. This observation was further confirmed via crystal violet staining, confocal laser scanning microscopy, and field emission-scanning electron microscopy. To disclose the underlying mechanisms, RNA-seq was applied. TF3 treatment significantly altered the transcriptomic profile of E. faecalis, as evidenced by identification of 248 differentially expressed genes (DEGs). Through functional annotation of these DEGs, several quorum-sensing pathways were found to be suppressed in TF3-treated cultures. Further, gene expression verification via real-time PCR confirmed the downregulation of gelE, sprE, and secY by TF3. These findings highlighted the ability of TF3 to impede E. faecalis biofilm formation, suggesting a novel preventive strategy against E. faecalis infections.


Assuntos
Antibacterianos , Biflavonoides , Biofilmes , Catequina , Enterococcus faecalis , Regulação Bacteriana da Expressão Gênica , Percepção de Quorum , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Enterococcus faecalis/efeitos dos fármacos , Enterococcus faecalis/genética , Percepção de Quorum/efeitos dos fármacos , Biflavonoides/farmacologia , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Antibacterianos/farmacologia , Catequina/farmacologia , Catequina/análogos & derivados , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Transcriptoma/efeitos dos fármacos , Perfilação da Expressão Gênica
17.
Food Res Int ; 190: 114650, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38945629

RESUMO

Various pathogens have the ability to grow on food matrices and instruments. This grow may reach to form biofilms. Bacterial biofilms are community of microorganisms embedded in extracellular polymeric substances (EPSs) containing lipids, DNA, proteins, and polysaccharides. These EPSs provide a tolerance and favorable living condition for microorganisms. Biofilm formations could not only contribute a risk for food safety but also have negative impacts on healthcare sector. Once biofilms form, they reveal resistances to traditional detergents and disinfectants, leading to cross-contamination. Inhibition of biofilms formation and abolition of mature biofilms is the main target for controlling of biofilm hazards in the food industry. Some novel eco-friendly technologies such as ultrasound, ultraviolet, cold plasma, magnetic nanoparticles, different chemicals additives as vitamins, D-amino acids, enzymes, antimicrobial peptides, and many other inhibitors provide a significant value on biofilm inhibition. These anti-biofilm agents represent promising tools for food industries and researchers to interfere with different phases of biofilms including adherence, quorum sensing molecules, and cell-to-cell communication. This perspective review highlights the biofilm formation mechanisms, issues associated with biofilms, environmental factors influencing bacterial biofilm development, and recent strategies employed to control biofilm-forming bacteria in the food industry. Further studies are still needed to explore the effects of biofilm regulation in food industries and exploit more regulation strategies for improving the quality and decreasing economic losses.


Assuntos
Biofilmes , Indústria Alimentícia , Microbiologia de Alimentos , Inocuidade dos Alimentos , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Percepção de Quorum/efeitos dos fármacos , Bactérias/efeitos dos fármacos , Bactérias/crescimento & desenvolvimento , Antibacterianos/farmacologia
18.
J Vis Exp ; (207)2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38884467

RESUMO

Bacteria detect local population numbers using quorum sensing, a method of cell-cell communication broadly utilized to control bacterial behaviors. In Vibrio species, the master quorum sensing regulators LuxR/HapR control hundreds of quorum sensing genes, many of which influence virulence, metabolism, motility, and more. Thiophenesulfonamides are potent inhibitors of LuxR/HapR that bind the ligand pocket in these transcription factors and block downstream quorum sensing gene expression. This class of compounds served as the basis for the development of a set of simple, robust, and educational procedures for college students to assimilate their chemistry and biology skills using a CURE model: course-based undergraduate research experience. Optimized protocols are described that comprise three learning stages in an iterative and multi-disciplinary platform to engage students in a year-long CURE: (1) design and synthesize new small molecule inhibitors based on the thiophenesulfonamide core, (2) use structural modeling to predict binding affinity to the target, and (3) assay the compounds for efficacy in microbiological assays against specific Vibrio LuxR/HapR proteins. The described reporter assay performed in E. coli successfully predicts the efficacy of the compounds against target proteins in the native Vibrio species.


Assuntos
Percepção de Quorum , Transativadores , Vibrio , Percepção de Quorum/efeitos dos fármacos , Vibrio/efeitos dos fármacos , Vibrio/química , Vibrio/metabolismo , Vibrio/genética , Transativadores/antagonistas & inibidores , Transativadores/genética , Transativadores/metabolismo , Transativadores/química , Proteínas Repressoras/antagonistas & inibidores , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Proteínas Repressoras/química , Sulfonamidas/farmacologia , Sulfonamidas/química , Tiofenos/química , Tiofenos/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Proteínas de Bactérias/antagonistas & inibidores , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/química
19.
Sci Rep ; 14(1): 13104, 2024 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-38849458

RESUMO

Bacteria employ quorum sensing as a remarkable mechanism for coordinating behaviors and communicating within their communities. In this study, we introduce a MATLAB Graphical User Interface (GUI) that offers a versatile platform for exploring the dynamics of quorum sensing. Our computational framework allows for the assessment of quorum sensing, the investigation of parameter dependencies, and the prediction of minimum biofilm thickness required for its initiation. A pivotal observation from our simulations underscores the pivotal role of the diffusion coefficient in quorum sensing, surpassing the influence of bacterial cell dimensions. Varying the diffusion coefficient reveals significant fluctuations in autoinducer concentration, highlighting its centrality in shaping bacterial communication. Additionally, our GUI facilitates the prediction of the minimum biofilm thickness necessary to trigger quorum sensing, a parameter contingent on the diffusion coefficient. This feature provides valuable insights into spatial constraints governing quorum sensing initiation. The interplay between production rates and cell concentrations emerges as another critical facet of our study. We observe that higher production rates or cell concentrations expedite quorum sensing, underscoring the intricate relationship between cell communication and population dynamics in bacterial communities. While our simulations align with mathematical models reported in the literature, we acknowledge the complexity of living organisms, emphasizing the value of our GUI for standardizing results and facilitating early assessments of quorum sensing. This computational approach offers a window into the environmental conditions conducive to quorum sensing initiation, encompassing parameters such as the diffusion coefficient, cell concentration, and biofilm thickness. In conclusion, our MATLAB GUI serves as a versatile tool for understanding the diverse aspects of quorum sensing especially for non-biologists. The insights gained from this computational framework advance our understanding of bacterial communication, providing researchers with the means to explore diverse ecological contexts where quorum sensing plays a pivotal role.


Assuntos
Biofilmes , Percepção de Quorum , Biofilmes/crescimento & desenvolvimento , Modelos Biológicos , Bactérias/metabolismo , Fenômenos Fisiológicos Bacterianos , Difusão , Interface Usuário-Computador , Simulação por Computador
20.
ACS Appl Mater Interfaces ; 16(25): 32824-32835, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38864267

RESUMO

Poor adsorption properties of nonadsorbing targets and competing adsorption of nontargets at a liquid interface always hamper the development of interface sensing techniques. There is a need to fabricate materials that are applicable to various interface assemblies and, meanwhile, could be employed as interfacial gating to improve the performance of interface sensing by separating, enriching, and recognizing targets at the liquid interface. Here, superhydrophobic zeolite imidazole frameworks-8@gold nanoparticles-1H,1H,2H,2H-perfluorodecanethiol (ZIF-8@GNPs-PFDT) with a static water contact angle (WCA) of 155° was constructed via electrostatic self-assembly and surface graft modification. The plasmonic metal-organic framework (PMOF) nanohybrid realized all-purpose self-assembly at air/liquid and liquid/liquid interfaces and also facilely assembled on the surface of liquid droplets, hydrogels, and foams. The self-assembled porous materials displayed the capability for separating, enriching, and recognizing analytes at various oil/water interfaces and thus could be used to adsorb nonadsorbing targets and block the competing adsorption of nontargets. The self-assembled ZIF-8@GNPs-PFDT structures were employed as a three-in-one interfacial gating to endow the excellent surface-enhanced Raman scattering (SERS) sensing capability and has become a promising tool for dye molecular analysis, oil/water separation, organic phase identification, and in situ cultivation and monitoring of bacterial quorum sensing (QS).


Assuntos
Ouro , Interações Hidrofóbicas e Hidrofílicas , Estruturas Metalorgânicas , Percepção de Quorum , Estruturas Metalorgânicas/química , Ouro/química , Nanopartículas Metálicas/química , Zeolitas/química , Adsorção , Propriedades de Superfície
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