Bicyclic brominated furanones: A new class of quorum sensing modulators that inhibit bacterial biofilm formation

Anti-virulence strategy is currently considered a promising approach to overcome the global threat of the antibiotic resistance. Among different bacterial virulence factors, the biofilm formation is recognized as one of the most relevant. Considering the high and growing percentage of multi-drug resistant infections that are biofilm-mediated, new therapeutic agents capable of counteracting the formation of biofilms are urgently required. In this scenario, a new series of 18 thiazole derivatives was efficiently synthesized and evaluated for its ability to inhibit biofilm formation against the Gram-positive bacterial reference strains Staphylococcus aureus ATCC 25923 and S. aureus ATCC 6538 and the Gram-negative strain Pseudomonas aeruginosa ATCC 15442. Most of the new compounds showed a marked selectivity against the Gram-positive strains. Remarkably, five compounds exhibited BIC50 values against S. aureus ATCC 25923 ranging from 1.0 to 9.1 µM. The new compounds, affecting the biofilm formation without any interference on microbial growth, can be considered promising lead compounds for the development of a new class of anti-virulence agents.

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Selenium and tellurium-based nanoparticles as interfering factors in quorum sensing-regulated processes: violacein production and bacterial biofilm formation

Metallomics ◽

10.1039/c9mt00044e ◽

2019 ◽

Vol 11 (6) ◽

pp. 1104-1114 ◽

Cited By ~ 6

Author(s):

Beatriz Gómez-Gómez ◽

Lucia Arregui ◽

Susana Serrano ◽

Antonio Santos ◽

Teresa Pérez-Corona ◽

...

Keyword(s):

Quorum Sensing ◽

Biofilm Formation ◽

Bacterial Biofilm ◽

Persistent Infections ◽

Violacein Production ◽

New Strategies

The effect of SeNPs and TeNPs on different processes regulated by QS such as violacein production and biofilm formation is presented. The data open new strategies for controlling persistent infections.

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Mutation of luxS Affects Biofilm Formation in Streptococcus mutans

Infection and Immunity ◽

10.1128/iai.71.4.1972-1979.2003 ◽

2003 ◽

Vol 71 (4) ◽

pp. 1972-1979 ◽

Cited By ~ 185

Author(s):

Justin Merritt ◽

Fengxia Qi ◽

Steven D. Goodman ◽

Maxwell H. Anderson ◽

Wenyuan Shi

Keyword(s):

Quorum Sensing ◽

Streptococcus Mutans ◽

Biofilm Formation ◽

Microscopic Analysis ◽

Homoserine Lactone ◽

Good Evidence ◽

Genome Project ◽

Bacterial Biofilm ◽

Wild Type

ABSTRACT Quorum sensing is a bacterial mechanism for regulating gene expression in response to changes in population density. Many bacteria are capable of acyl-homoserine lactone-based or peptide-based intraspecies quorum sensing and luxS-dependent interspecies quorum sensing. While there is good evidence about the involvement of intraspecies quorum sensing in bacterial biofilm, little is known about the role of luxS in biofilm formation. In this study, we report for the first time that luxS-dependent quorum sensing is involved in biofilm formation of Streptococcus mutans. S. mutans is a major cariogenic bacterium in the multispecies bacterial biofilm commonly known as dental plaque. An ortholog of luxS for S. mutans was identified using the data available in the S. mutans genome project (http://www.genome.ou.edu/smutans.html ). Using an assay developed for the detection of the LuxS-associated quorum sensing signal autoinducer 2 (AI-2), it was demonstrated that this ortholog was able to complement the luxS negative phenotype of Escherichia coli DH5α. It was also shown that AI-2 is indeed produced by S. mutans. AI-2 production is maximal during mid- to late-log growth in batch culture. Mutant strains devoid of the luxS gene were constructed and found to be defective in producing the AI-2 signal. There are also marked phenotypic differences between the wild type and the luxS mutants. Microscopic analysis of in vitro-grown biofilm structure revealed that the luxS mutant biofilms adopted a much more granular appearance, rather than the relatively smooth, confluent layer normally seen in the wild type. These results suggest that LuxS-dependent signal may play an important role in biofilm formation of S. mutans.

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Use of Quorum Sensing Inhibition Strategies to Control Microfouling

Marine Drugs ◽

10.3390/md19020074 ◽

2021 ◽

Vol 19 (2) ◽

pp. 74

Author(s):

Andrea Muras ◽

Ana Parga ◽

Celia Mayer ◽

Ana Otero

Keyword(s):

Quorum Sensing ◽

Biofilm Formation ◽

Communication Systems ◽

Culture Medium ◽

Homoserine Lactone ◽

Bacterial Biofilm ◽

Screening Methods ◽

Time Saving ◽

Quorum Sensing Inhibition

Interfering with the quorum sensing bacterial communication systems has been proposed as a promising strategy to control bacterial biofilm formation, a key process in biofouling development. Appropriate in vitro biofilm-forming bacteria models are needed to establish screening methods for innovative anti-biofilm and anti-microfouling compounds. Four marine strains, two Pseudoalteromonas spp. and two Vibrio spp., were selected and studied with regard to their biofilm-forming capacity and sensitivity to quorum sensing (QS) inhibitors. Biofilm experiments were performed using two biofilm cultivation and quantification methods: the xCELLigence® system, which allows online monitoring of biofilm formation, and the active attachment model, which allows refreshment of the culture medium to obtain a strong biofilm that can be quantified with standard staining methods. Although all selected strains produced acyl-homoserine-lactone (AHL) QS signals, only the P. flavipulchra biofilm, measured with both quantification systems, was significantly reduced with the addition of the AHL-lactonase Aii20J without a significant effect on planktonic growth. Two-species biofilms containing P. flavipulchra were also affected by the addition of Aii20J, indicating an influence on the target bacterial strain as well as an indirect effect on the co-cultured bacterium. The use of xCELLigence® is proposed as a time-saving method to quantify biofilm formation and search for eco-friendly anti-microfouling compounds based on quorum sensing inhibition (QSI) strategies. The results obtained from these two in vitro biofilm formation methods revealed important differences in the response of biosensor bacteria to culture medium and conditions, indicating that several strains should be used simultaneously for screening purposes and the cultivation conditions should be carefully optimized for each specific purpose.

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Design, Synthesis, and Evaluation of Alkyl-Quinoxalin-2(1H)-One Derivatives as Anti-Quorum Sensing Molecules, Inhibiting Biofilm Formation in Aeromonas caviae Sch3

Molecules ◽

10.3390/molecules23123075 ◽

2018 ◽

Vol 23 (12) ◽

pp. 3075 ◽

Cited By ~ 1

Author(s):

René Blöcher ◽

Ariel Rodarte Ramírez ◽

Graciela Castro-Escarpulli ◽

Everardo Curiel-Quesada ◽

Alicia Reyes-Arellano

Keyword(s):

Carboxylic Acid ◽

Quorum Sensing ◽

Biofilm Formation ◽

Bacterial Biofilm ◽

Alternative Methods ◽

Resistant Bacteria ◽

Bacterial Strains ◽

Design Synthesis ◽

Bacterial Communication ◽

Aeromonas Caviae

With the increasing antibiotic resistance of bacterial strains, alternative methods for infection control are in high demand. Quorum sensing (QS) is the bacterial communication system based on small molecules. QS is enables bacterial biofilm formation and pathogenic development. The interruption of QS has become a target for drug discovery, but remains in the early experimental phase. In this study, we synthesized a set of six compounds based on a scaffold (alkyl-quinoxalin-2(1H)-one), new in the anti-QS of Gram-negative bacteria Aeromonas caviae Sch3. By quantifying biofilm formation, we were able to monitor the effect of these compounds from concentrations of 1 to 100 µM. Significant reduction in biofilm formation was achieved by 3-hexylylquinoxalin-2(1H)-one (11), 3-hexylylquinoxalin-2(1H)-one-6-carboxylic acid (12), and 3-heptylylquinoxalin-2(1H)-one-6-carboxylic acid (14), ranging from 11% to 59% inhibition of the biofilm. This pilot study contributes to the development of anti-QS compounds to overcome the clinical challenge of resistant bacteria strains.

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Acetic Acid Acts as a Volatile Signal To Stimulate Bacterial Biofilm Formation

mBio ◽

10.1128/mbio.00392-15 ◽

2015 ◽

Vol 6 (3) ◽

Cited By ~ 42

Author(s):

Yun Chen ◽

Kevin Gozzi ◽

Fang Yan ◽

Yunrong Chai

Keyword(s):

Acetic Acid ◽

Bacillus Subtilis ◽

Quorum Sensing ◽

Biofilm Formation ◽

Molecular Mechanisms ◽

Biological Activities ◽

Bacterial Biofilm ◽

Acetic Acid Production ◽

Content Type ◽

Metabolic Signal

ABSTRACTVolatiles are small air-transmittable chemicals with diverse biological activities. In this study, we showed that volatiles produced by the bacteriumBacillus subtilishad a profound effect on biofilm formation of neighboringB. subtiliscells that grew in proximity but were physically separated. We further demonstrated that one such volatile, acetic acid, is particularly potent in stimulating biofilm formation. Multiple lines of genetic evidence based onB. subtilismutants that are defective in either acetic acid production or transportation suggest thatB. subtilisuses acetic acid as a metabolic signal to coordinate the timing of biofilm formation. Lastly, we investigated howB. subtiliscells sense and respond to acetic acid in regulating biofilm formation. We showed the possible involvement of three sets of genes (ywbHG,ysbAB, andyxaKC), all encoding putative holin-antiholin-like proteins, in cells responding to acetic acid and stimulating biofilm formation. All three sets of genes were induced by acetate. A mutant with a triple mutation of those genes showed a severe delay in biofilm formation, whereas a strain overexpressingywbHGshowed early and robust biofilm formation. Results of our studies suggest thatB. subtilisand possibly other bacteria use acetic acid as a metabolic signal to regulate biofilm formation as well as a quorum-sensing-like airborne signal to coordinate the timing of biofilm formation by physically separated cells in the community.IMPORTANCEVolatiles are small, air-transmittable molecules produced by all kingdoms of organisms including bacteria. Volatiles possess diverse biological activities and play important roles in bacteria-bacteria and bacteria-host interactions. Although volatiles can be used as a novel and important way of cell-cell communication due to their air-transmittable nature, little is known about how the volatile-mediated signaling mechanism works. In this study, we demonstrate that the bacteriumBacillus subtilisuses one such volatile, acetic acid, as a quorum-sensing-like signal to coordinate the timing of the formation of structurally complex cell communities, also known as biofilms. We further characterized the molecular mechanisms of howB. subtilisresponds to acetic acid in stimulating biofilm formation. Our study also suggests that acetic acid may be used as a volatile signal for cross-species communication.

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Quorum sensing inhibitory effects of vanillin on the biofilm formation of Pseudomonas fluorescens P07 by transcriptome analysis

SDRP Journal of Food Science & Technology ◽

10.25177/jfst.5.7.ra.10686 ◽

2021 ◽

Vol 5 (7) ◽

pp. 275-292

Author(s):

Ting Ding ◽

◽

Yong Li

Keyword(s):

Quorum Sensing ◽

Pseudomonas Fluorescens ◽

Transcriptome Analysis ◽

Biofilm Formation ◽

Homoserine Lactone ◽

Bacterial Biofilm ◽

Inhibitory Effects ◽

Swarming Motility ◽

Physiological Processes ◽

Spoilage Bacterium

Pseudomonas fluorescens is an important psychrotrophic food-spoilage bacterium. Quorum sensing (QS) enables bacteria to control various physiological processes. Hence, targeting bacterial QS would be a novel method to improve food quality. In this study, P. fluorescens P07 was treated with vanillin, which showed strong QS inhibitory activity, and its resultant effects on swarming motility, biofilm formation, and extracellular polymeric substance (EPS) secretion were measured. The mechanisms underlying the inhibitory effects were then explored by transcriptomic analysis. The results showed that vanillin had inhibitory effects on swarming motility, biofilm formation, N-acyl-L-homoserine Lactone (AHLs) and EPS secretion of P. fluorescens P07. The result of transcriptionomic tests indicated that the decrease in bacterial biofilm formation was probably due to the influence of vanillin on mobility, adhesion, chemotaxis, EPS secretion, and QS system of the bacteria. Keywords: Pseudomonas fluorescens, quorum sensing, biofilm formation, transcriptome analysis, swarming motility

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PEA polymer-coated nanotopography delivers solid-state BMP2, enhances mesenchymal stem cell adhesion, prevents bacterial biofilm formation and protects cells from quorum sensing virulence factors

10.1101/2020.09.17.302455 ◽

2020 ◽

Author(s):

Laila A. Damiati ◽

Monica P. Tsimbouri ◽

Mark Ginty ◽

Virginia Llopis Hernandez ◽

Peter Childs ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Stem Cell ◽

Quorum Sensing ◽

Mesenchymal Stem Cell ◽

Biofilm Formation ◽

Major Complication ◽

Ethyl Acrylate ◽

Bacterial Biofilm ◽

Bone Morphogenetic Protein 2 ◽

Signalling Molecules

AbstractPost-operative infection is a major complication in patients recovering from orthopaedic surgery. As such, there is a clinical need to develop biomaterials for use in regenerative surgery that can promote mesenchymal stem cell (MSC) osteospecific differentiation and that can prevent infection caused by biofilm-forming pathogens. Nanotopographical approaches to pathogen control are being identified, including in orthopaedic materials such as titanium and its alloys. These topographies use high aspect ratio nanospikes or nanowires to prevent bacterial adhesion but these features puncture adhering cells, thus also reducing MSC adhesion. Here, we use a poly(ethyl acrylate) (PEA) polymer coating on titanium nanowires to spontaneously organise fibronectin (FN) and to deliver bone morphogenetic protein 2 (BMP2) to enhance MSC adhesion and osteospecific signalling. This nanotopography when combined with the PEA coating enhanced osteogenesis and reduced adhesion of Pseudomonas aeruginosa in culture. Using a novel MSC–Pseudomonas aeruginosa co-culture, we also show that the coated nanotopographies protect MSCs from cytotoxic quorum sensing and signalling molecules. We conclude that the PEA polymer-coated nanotopography can both support MSCs and prevent pathogens from adhering to a biomaterial surface, thus protecting from biofilm formation and bacterial infection and supporting osteogenic repair.

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CRISPR-cas3 of Salmonella Upregulates Bacterial Biofilm Formation and Virulence to Host Cells by Targeting Quorum-Sensing Systems

Pathogens ◽

10.3390/pathogens9010053 ◽

2020 ◽

Vol 9 (1) ◽

pp. 53 ◽

Cited By ~ 6

Author(s):

Luqing Cui ◽

Xiangru Wang ◽

Deyu Huang ◽

Yue Zhao ◽

Jiawei Feng ◽

...

Keyword(s):

Quorum Sensing ◽

Biofilm Formation ◽

Bacterial Biofilm ◽

Host Cells ◽

Microbial Pathogens ◽

Bacterial Invasion ◽

Type I ◽

Salmonella Enterica Serovar Enteritidis ◽

Sensing Systems ◽

Type Three Secretion System

Salmonella is recognized as one of the most common microbial pathogens worldwide. The bacterium contains the clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated (Cas) systems, providing adaptive immunity against invading foreign nucleic acids. Previous studies suggested that certain bacteria employ the Cas proteins of CRISPR-Cas systems to target their own genes, which also alters the virulence during invasion of mammals. However, whether CRISPR-Cas systems in Salmonella have similar functions during bacterial invasion of host cells remains unknown. Here, we systematically analyzed the genes that are regulated by Cas3 in a type I-E CRISPR-Cas system and the virulence changes due to the deletion of cas3 in Salmonella enterica serovar Enteritidis. Compared to the cas3 gene wild-type (cas3 WT) Salmonella strain, cas3 deletion upregulated the lsrFGBE genes in lsr (luxS regulated) operon related to quorum sensing (QS) and downregulated biofilm-forming-related genes and Salmonella pathogenicity island 1 (SPI-1) genes related to the type three secretion system (T3SS). Consistently, the biofilm formation ability was downregulated in the cas3 deletion mutant (Δcas3). The bacterial invasive and intracellular capacity of Δcas3 to host cells was also reduced, thereby increasing the survival of infected host cells and live chickens. By the transcriptome-wide screen (RNA-Seq), we found that the cas3 gene impacts a series of genes related to QS, the flagellum, and SPI-1-T3SS system, thereby altering the virulence phenotypes. As QS SPI-1-T3SS and CRISPR-Cas systems are widely distributed in the bacteria kingdom, our findings extend our understanding of virulence regulation and pathogenicity in mammalian hosts for Salmonella and potentially other bacteria.

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