Disruption of Biofilm Formation by the Human Pathogen Acinetobacter baumannii Using Engineered Quorum-Quenching Lactonases

Chow, Jeng Yeong; Yang, Yuanyong; Tay, Song Buck; Chua, Kim Lee; Yew, Wen Shan

doi:10.1128/aac.02410-13

Cited by 93 publications

(80 citation statements)

References 19 publications

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“…Nevertheless, the extent of biofilm disruption for both enzymes is not proportional to their efficacy against 3-OH-C 10 -HSL. The turnover rate (k cat ) of the GKL E101G/R230C mutant is six times faster than wild-type GKL against 3-OH-C 10 -HSL 14 . However, the difference in the extent of biofilm disruption between the enzymes is only two-fold.…”

Section: Representative Resultsmentioning

confidence: 94%

“…Both enzymes have been shown to demonstrate lactonase activity against 3-hydroxy-decanoyl-L-homoserine lactone (3-OH-C 10 -HSL), the major quorum molecule used by A. baumannii S1 14 . For valid assessment of biofilm disruption, their respective catalytically inactive enzymes (previously shown to not sequester AHL ligands) were also included as immediate controls (GKL D266N mutant and GKL E101G/R230C/D266N mutant).…”

Section: Representative Resultsmentioning

confidence: 99%

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Anti-virulent Disruption of Pathogenic Biofilms using Engineered Quorum-quenching Lactonases

Tay

Chow

et al. 2016

JoVE

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The rapid emergence of multi-drug resistant bacteria has accelerated the need for novel therapeutic approaches to counter life-threatening infections. The persistence of bacterial infection is often associated with quorum-sensing-mediated biofilm formation. Thus, the disruption of this signaling circuit presents an attractive anti-virulence strategy. Quorum-quenching lactonases have been reported to be effective disrupters of quorum-sensing circuits. However, there have been very few reports of the effective use of these enzymes in disrupting bacterial biofilm formation. This protocol describes a method to disrupt biofilm formation in a clinically relevant A. baumannii S1 strain through the use of an engineered quorum-quenching lactonase. Acinetobacter baumannii is a major human pathogen implicated in serious hospital-acquired infections globally and its virulence is attributed predominantly to its biofilm's tenacity. The engineered lactonase treatment achieved significant A. baumannii S1 biofilm reduction. This study also showed the possibility of using engineered quorum-quenching enzymes in future treatment of biofilm-mediated bacterial diseases. Lastly, the method may be used to evaluate the competency of promising quorum-quenching enzymes. Video LinkThe video component of this article can be found at

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Section: Representative Resultsmentioning

confidence: 94%

Section: Representative Resultsmentioning

confidence: 99%

Anti-virulent Disruption of Pathogenic Biofilms using Engineered Quorum-quenching Lactonases

Tay

Chow

et al. 2016

JoVE

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“…Because DsbA/B is not essential for bacterial survival (51) but is required for virulence (17), DsbA/B is a target for the development of novel anti-virulence agents against Gram-negative bacteria (17). For example, biofilm formation is essential for colonization and infection by A. baumannii (13,74,75). Interference with this process by inhibiting DsbA could impair the ability of bacteria to establish infection.…”

Section: Discussionmentioning

confidence: 99%

Structure of the Acinetobacter baumannii Dithiol Oxidase DsbA Bound to Elongation Factor EF-Tu Reveals a Novel Protein Interaction Site

Premkumar

Kurth

Duprez

et al. 2014

Journal of Biological Chemistry

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Background: DsbA is a master virulence determinant of bacterial pathogens and a target for antivirulence drugs. Results: AbDsbA is a class I dithiol oxidase that binds EF-Tu-derived and DsbB-derived peptides on different enzyme surfaces. Conclusion: Discovery of high affinity peptide interaction sites provides a platform for inhibitor design. Significance: AbDsbA inhibitors could have anti-biofilm activity against multidrug resistant Acinetobacter baumannii.

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“…The ability of this pathogen to develop antibiotic resistance is a public health issue worldwide. Its main QS signaling molecule has been identified as N-3-hydroxy-dodecanoylhomoserine lactone, and in this pathogen, QS regulates biofilm formation and the expression of drug-resistance genes [16][17][18].…”

Section: Biosensing Technologies For the Detection Of Pathogens -A Prmentioning

confidence: 99%

Detection and Control of Indoor Airborne Pathogenic Bacteria by Biosensors Based on Quorum Sensing Chemical Language: Bio-Tools, Connectivity Apps and Intelligent Buildings

Ibacache-Quiroga¹,

Romo²,

Díaz-Viciedo³

et al. 2018

Biosensing Technologies for the Detection of Pathogens - A Prospective Way for Rapid Analysis

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Nowadays, lifestyles and climate change lead people to spend long periods in indoors spaces, where reduced ventilation and artificial light favor the concentration and spread of airborne pathogenic microorganisms. Current procedures for microbiological air evaluation are based on air sampling coupled to traditional microbiological culturedependent methods such as biochemical tests and molecular rDNA 16S sequencing. These techniques generate an important delay in the application of prevention and control measures. This chapter presents whole cell-based biosensors that are able to detect quorum sensing signaling molecules produced by airborne pathogenic bacteria as a tool for indoor air monitoring. Furthermore, a general biosensor model is proposed. In this model, in vivo biosensors technology can be connected to online applications (Apps), being part of intelligent buildings, in order to reduce airborne pathogenic bacteria concentration and dissemination.

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Disruption of Biofilm Formation by the Human Pathogen Acinetobacter baumannii Using Engineered Quorum-Quenching Lactonases

Cited by 93 publications

References 19 publications

Anti-virulent Disruption of Pathogenic Biofilms using Engineered Quorum-quenching Lactonases

Anti-virulent Disruption of Pathogenic Biofilms using Engineered Quorum-quenching Lactonases

Structure of the Acinetobacter baumannii Dithiol Oxidase DsbA Bound to Elongation Factor EF-Tu Reveals a Novel Protein Interaction Site

Detection and Control of Indoor Airborne Pathogenic Bacteria by Biosensors Based on Quorum Sensing Chemical Language: Bio-Tools, Connectivity Apps and Intelligent Buildings

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