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

Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3075 ◽  
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.

scholarly journals Tetracycline Induces the Formation of Biofilm of Bacteria from Different Phases of Wastewater Treatment

Processes ◽  
2020 ◽  
Vol 8 (8) ◽  
pp. 989
Author(s):  
Tereza Stachurová ◽  
Kateřina Malachová ◽  
Jaroslav Semerád ◽  
Meta Sterniša ◽  
Zuzana Rybková ◽  
...  
Keyword(s):  
Wastewater Treatment ◽  
Relative Abundance ◽  
Resistance Genes ◽  
Biofilm Formation ◽  
Treatment Plant ◽  
Bacterial Biofilm ◽  
Resistant Bacteria ◽  
Bacterial Strains ◽  
Wastewater Treatment Process ◽  
Sedimentation Tank

The study monitored the effect of tetracycline on bacterial biofilm formation and compared biofilm formation by resistant bacterial strains in different phases of the wastewater treatment process in wastewater treatment plant (WWTP). The crystal violet staining method was used to evaluate the biofilm formation. Biofilm-related bacterial properties were characterized by hydrophobicity, autoaggregation and motility tests. The relative abundance of tetracycline resistance genes (tetW, tetM, tetO, tetA and tetB) in wastewaters were subsequently quantified using qPCR. The results show that the isolates from the nitrification tank produce biofilm with up to 10 times greater intensity relative to the isolates from the sedimentation tank. In isolates of Aeromonas sp. from the nitrification tank, increased biofilm production in the occurrence of tetracycline from a concentration of 0.03125 µg/mL was observed. The tetW gene showed the highest relative abundance out of all the tested genes. From the sampling points, its abundance was the highest in the sedimentation tank of the WWTP. Based on these results, it can be assumed that resistant bacteria are able to form a biofilm and sub-inhibitory tetracycline concentrations induce biofilm formation. WWTPs thus represent a reservoir of antibiotic resistance genes and contribute to the spread of resistance in the natural environment.

Inhibition of Bacterial Biofilm Formation by Phytotherapeutics with Focus on Overcoming Antimicrobial Resistance

2020 ◽  
Vol 26 (24) ◽  
pp. 2807-2816 ◽  
Author(s):  
Yun Su Jang ◽  
Tímea Mosolygó
Keyword(s):  
Antimicrobial Resistance ◽  
Biofilm Formation ◽  
Antimicrobial Agents ◽  
Bacterial Biofilm ◽  
Experimental Investigations ◽  
Resistant Bacteria ◽  
Salmonella Spp ◽  
Food Borne ◽  
High Prevalence ◽  
Scientific Attention

: Bacteria within biofilms are more resistant to antibiotics and chemical agents than planktonic bacteria in suspension. Treatment of biofilm-associated infections inevitably involves high dosages and prolonged courses of antimicrobial agents; therefore, there is a potential risk of the development of antimicrobial resistance (AMR). Due to the high prevalence of AMR and its association with biofilm formation, investigation of more effective anti-biofilm agents is required. : From ancient times, herbs and spices have been used to preserve foods, and their antimicrobial, anti-biofilm and anti-quorum sensing properties are well known. Moreover, phytochemicals exert their anti-biofilm properties at sub-inhibitory concentrations without providing the opportunity for the emergence of resistant bacteria or harming the host microbiota. : With increasing scientific attention to natural phytotherapeutic agents, numerous experimental investigations have been conducted in recent years. The present paper aims to review the articles published in the last decade in order to summarize a) our current understanding of AMR in correlation with biofilm formation and b) the evidence of phytotherapeutic agents against bacterial biofilms and their mechanisms of action. The main focus has been put on herbal anti-biofilm compounds tested to date in association with Staphylococcus aureus, Pseudomonas aeruginosa and food-borne pathogens (Salmonella spp., Campylobacter spp., Listeria monocytogenes and Escherichia coli).

scholarly journals The Interaction of N-Acetylcysteine and Serum Transferrin Promotes Bacterial Biofilm Formation

2018 ◽  
Vol 45 (4) ◽  
pp. 1399-1409 ◽  
Author(s):  
Supeng Yin ◽  
Bei Jiang ◽  
Guangtao Huang ◽  
Yulong Zhang ◽  
Bo You ◽  
...  
Keyword(s):  
Human Serum ◽  
Biofilm Formation ◽  
Laser Scanning ◽  
Serum Proteins ◽  
Venous Catheter ◽  
Bacterial Biofilm ◽  
Laser Scanning Microscopy ◽  
Confocal Laser ◽  
Bacterial Strains

Background/Aims: N-acetylcysteine (NAC) is a novel and promising agent with activity against bacterial biofilms. Human serum also inhibits biofilm formation by some bacteria. We tested whether the combination of NAC and human serum offers greater anti-biofilm activity than either agent alone. Methods: Microtiter plate assays and confocal laser scanning microscopy were used to evaluate bacterial biofilm formation in the presence of NAC and human serum. qPCR was used to examine expression of selected biofilm-associated genes. Extracellular matrix (ECM) was observed by transmission electron microscopy. The antioxidants GSH or ascorbic acid were used to replace NAC, and human transferrin, lactoferrin, or bovine serum albumin were used to replace serum proteins in biofilm formation assays. A rat central venous catheter model was developed to evaluate the effect of NAC on biofilm formation in vivo. Results: NAC and serum together increased biofilm formation by seven different bacterial strains. In Staphylococcus aureus, expression of genes for some global regulators and for genes in the ica-dependent pathway increased markedly. In Pseudomonas aeruginosa, transcription of las, the PQS quorum sensing (QS) systems, and the two-component system GacS/GacA increased significantly. ECM production by S. aureus and P. aeruginosa was also enhanced. The potentiation of biofilm formation is due mainly to interaction between NAC and transferrin. Intravenous administration of NAC increased colonization by S. aureus and P. aeruginosa on implanted catheters. Conclusions: NAC used intravenously or in the presence of blood increases bacterial biofilm formation rather than inhibits it.

scholarly journals Synthesis, In Silico, and In Vitro Evaluation of Long Chain Alkyl Amides from 2-Amino-4-Quinolone Derivatives as Biofilm Inhibitors

Molecules ◽  
2019 ◽  
Vol 24 (2) ◽  
pp. 327 ◽  
Author(s):  
Mariana Espinosa-Valdés ◽  
Sara Borbolla-Alvarez ◽  
Ana Delgado-Espinosa ◽  
Juan Sánchez-Tejeda ◽  
Anabelle Cerón-Nava ◽  
...  
Keyword(s):  
Quorum Sensing ◽  
Biofilm Formation ◽  
Active Sites ◽  
Multidrug Resistant ◽  
Health Concern ◽  
Resistant Bacteria ◽  
Biofilm Inhibition ◽  
Amide Derivatives ◽  
Long Chain

Infection from multidrug resistant bacteria has become a growing health concern worldwide, increasing the need for developing new antibacterial agents. Among the strategies that have been studied, biofilm inhibitors have acquired relevance as a potential source of drugs that could act as a complement for current and new antibacterial therapies. Based on the structure of 2-alkyl-3-hydroxy-4-quinolone and N-acylhomoserine lactone, molecules that act as mediators of quorum sensing and biofilm formation in Pseudomonas aeruginosa, we designed, prepared, and evaluated the biofilm inhibition properties of long chain amide derivatives of 2-amino-4-quinolone in Staphylococcus aureus and P. aeruginosa. All compounds had higher biofilm inhibition activity in P. aeruginosa than in S. aureus. Particularly, compounds with an alkyl chain of 12 carbons exhibited the highest inhibition of biofilm formation. Docking scores and molecular dynamics simulations of the complexes of the tested compounds within the active sites of proteins related to quorum sensing had good correlation with the experimental results, suggesting the diminution of biofilm formation induced by these compounds could be related to the inhibition of these proteins.

scholarly journals Anti-quorum Sensing and Protective Efficacies of Naringin Against Aeromonas hydrophila Infection in Danio rerio

2020 ◽  
Vol 11 ◽  
Author(s):  
Ramanathan Srinivasan ◽  
Kannan Rama Devi ◽  
Sivasubramanian Santhakumari ◽  
Arunachalam Kannappan ◽  
Xiaomeng Chen ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Quorum Sensing ◽  
Aeromonas Hydrophila ◽  
Biofilm Formation ◽  
Bacterial Load ◽  
Antibiotic Resistance Genes ◽  
Alternative Methods ◽  
Zebrafish Model ◽  
Virulence Gene Expression

It is now well known that the quorum sensing (QS) mechanism coordinates the production of several virulence factors and biofilm formation in most pathogenic microorganisms. Aeromonas hydrophila is a prime pathogen responsible for frequent outbreaks in aquaculture settings. Recent studies have also continuously reported that A. hydrophila regulates virulence factor production and biofilm formation through the QS system. In addition to the presence of antibiotic resistance genes, biofilm-mediated antibiotic resistance increases the severity of A. hydrophila infections. To control the bacterial pathogenesis and subsequent infections, targeting the QS mechanism has become one of the best alternative methods. Though very few compounds were identified as QS inhibitors against A. hydrophila, to date, the screening and identification of new and effective natural QS inhibitors is a dire necessity to control the infectious A. hydrophila. The present study endorses naringin (NA) as an anti-QS and anti-infective agent against A. hydrophila. Initially, the NA showed a concentration-dependent biofilm reduction against A. hydrophila. Furthermore, the results of microscopic analyses and quantitative virulence assays displayed the promise of NA as a potential anti-QS agent. Subsequently, the downregulation of ahh1, aerA, lip and ahyB validate the interference of NA in virulence gene expression. Furthermore, the in vivo assays were carried out in zebrafish model system to evaluate the anti-infective potential of NA. The outcome of the immersion challenge assay showed that the recovery rate of the zebrafish has substantially increased upon treatment with NA. Furthermore, the quantification of the bacterial load upon NA treatment showed a decreased level of bacterial counts in zebrafish when compared to the untreated control. Moreover, the NA treatment averts the pathogen-induced histoarchitecture damages in vital organs of zebrafish, compared to their respective controls. The current study has thus analyzed the anti-QS and anti-infective capabilities of NA and could be employed to formulate effective treatment measures against A. hydrophila infections.

scholarly journals IgY Targeting Bacterial Quorum-Sensing Molecules in Implant-Associated Infections

Molecules ◽  
2020 ◽  
Vol 25 (17) ◽  
pp. 4027
Author(s):  
Ulrike Dapunt ◽  
Birgit Prior ◽  
Christopher Oelkrug ◽  
Jan Philippe Kretzer
Keyword(s):  
Quorum Sensing ◽  
Staphylococcus Epidermidis ◽  
Biofilm Formation ◽  
Major Complication ◽  
Underlying Mechanism ◽  
Bacterial Communication ◽  
Bacterial Quorum Sensing ◽  
Polysaccharide Intercellular Adhesion ◽  
Bacterial Quorum ◽  
Treatment Alternatives

Background: Implant-associated infections are still a major complication in the field of orthopedics. Bacteria can form biofilms on implant surfaces, making them more difficult to detect and treat. Since standard antibiotic therapy is often impaired in biofilm infections, particular interest is directed towards finding treatment alternatives. Biofilm-formation is a well-organized process during which bacteria communicate via quorum-sensing molecules (QSM). The aim of this study was to inhibit bacterial communication by directing avian IgY against specific QSM. Methods: Chicken were immunized against the following QSM: (1) AtlE, a member of the autolysin family which mediates attachment to a surface in Staphylococcus epidermidis; (2) GroEL, the bacterial heat shock protein; (3) PIA (polysaccharide intercellular adhesion), which is essential for cell–cell adhesion in biofilms. Staphylococcus epidermidis biofilms were grown and inhibition of biofilm-formation by IgYs was evaluated. Additionally, human osteoblasts were cultivated and biocompatibility of IgYs was tested. Results: We were able to demonstrate that all IgYs reduced biofilm-formation, also without prior immunization. Therefore, the response was probably not specific with regard to the QSM. Osteoblasts were activated by all IgYs which was demonstrated by microscopy and an increased release of IL-8. Conclusions: In conclusion, avian IgY inhibits biofilm-formation, though the underlying mechanism is not yet clear. However, adverse effects on local tissue cells (osteoblasts) were also observed.

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

Metallomics ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 1104-1114 ◽  
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.

scholarly journals Identification of FDA-Approved Drugs as Antivirulence Agents Targeting the pqs Quorum-Sensing System of Pseudomonas aeruginosa

2018 ◽  
Vol 62 (11) ◽  
Author(s):  
Francesca D'Angelo ◽  
Valerio Baldelli ◽  
Nigel Halliday ◽  
Paolo Pantalone ◽  
Fabio Polticelli ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Biofilm Formation ◽  
Antifungal Drugs ◽  
Phenotypic Characterization ◽  
Resistant Bacteria ◽  
Gram Positive ◽  
Active Inhibitor ◽  
Content Type ◽  
Approved Drugs

ABSTRACT The long-term use of antibiotics has led to the emergence of multidrug-resistant bacteria. A promising strategy to combat bacterial infections aims at hampering their adaptability to the host environment without affecting growth. In this context, the intercellular communication system quorum sensing (QS), which controls virulence factor production and biofilm formation in diverse human pathogens, is considered an ideal target. Here, we describe the identification of new inhibitors of the pqs QS system of the human pathogen Pseudomonas aeruginosa by screening a library of 1,600 U.S. Food and Drug Administration-approved drugs. Phenotypic characterization of ad hoc engineered strains and in silico molecular docking demonstrated that the antifungal drugs clotrimazole and miconazole, as well as an antibacterial compound active against Gram-positive pathogens, clofoctol, inhibit the pqs system, probably by targeting the transcriptional regulator PqsR. The most active inhibitor, clofoctol, specifically inhibited the expression of pqs-controlled virulence traits in P. aeruginosa, such as pyocyanin production, swarming motility, biofilm formation, and expression of genes involved in siderophore production. Moreover, clofoctol protected Galleria mellonella larvae from P. aeruginosa infection and inhibited the pqs QS system in P. aeruginosa isolates from cystic fibrosis patients. Notably, clofoctol is already approved for clinical treatment of pulmonary infections caused by Gram-positive bacterial pathogens; hence, this drug has considerable clinical potential as an antivirulence agent for the treatment of P. aeruginosa lung infections.

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

2014 ◽  
Vol 22 (4) ◽  
pp. 1313-1317 ◽  
Author(s):  
Sijie Yang ◽  
Osama A. Abdel-Razek ◽  
Fei Cheng ◽  
Debjyoti Bandyopadhyay ◽  
Gauri S. Shetye ◽  
...  
Keyword(s):  
Quorum Sensing ◽  
Biofilm Formation ◽  
Bacterial Biofilm ◽  
New Class ◽  
Brominated Furanones

Characterization of two LuxI/R homologs in Pantoea ananatis LMG 2665T

2016 ◽  
Vol 62 (11) ◽  
pp. 893-903 ◽  
Author(s):  
Siphathele Sibanda ◽  
Jacques Theron ◽  
Divine Y. Shyntum ◽  
Lucy N. Moleleki ◽  
Teresa A. Coutinho
Keyword(s):  
Quorum Sensing ◽  
Genome Sequence ◽  
Biofilm Formation ◽  
Biological Significance ◽  
Bacterial Strains ◽  
Pantoea Ananatis ◽  
Ecological Fitness ◽  
Host Interactions

Quorum sensing (QS) plays an important role in the regulation of bacteria–host interactions and ecological fitness in many bacteria. In this study, 2 luxI/R homologs, namely eanI/eanR and rhlI/rhlR, were identified in the genome sequence of Pantoea ananatis LMG 2665T. To determine a role for these luxI/R homologs in pathogenicity and biofilm formation, mutant bacterial strains lacking either eanI/R or rhlI/R and both of these homologs were generated. The results indicated that both the RhlI/R and EanI/R systems are required for pathogenicity and biofilm formation in strain LMG 2665T. This is the first study to characterize the biological significance of the RhlI/R QS system in P. ananatis.

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