Engineering quorum quenching enzymes: progress and perspectives

Murugayah, Shereen Asha; Gerth, Monica L.

doi:10.1042/bst20180165

Cited by 51 publications

(40 citation statements)

References 61 publications

(63 reference statements)

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“…QS inhibitors fall into two categories: QQ enzymes and certain chemicals extracted from natural resources or obtained by chemical synthesis [ 46 , 47 , 48 , 49 ]. In isolating QQ enzymes from bacteria, it has been confirmed that there are a variety of strains presenting QS signal inactivation capabilities in different microbial genera [ 50 , 51 , 52 ].…”

Section: Discussionmentioning

confidence: 99%

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Quorum Quenching in a Novel Acinetobacter sp. XN-10 Bacterial Strain against Pectobacterium carotovorum subsp. carotovorum

et al. 2020

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Quorum sensing (QS) is a cell density-dependent mechanism that regulates the expression of specific genes in microbial cells. Quorum quenching (QQ) is a promising strategy for attenuating pathogenicity by interfering with the QS system of pathogens. N-Acyl-homoserine lactones (AHLs) act as signaling molecules in many Gram-negative bacterial pathogens and have received wide attention. In this study, a novel, efficient AHL-degrading bacterium, Acinetobacter sp. strain XN-10, was isolated from agricultural contaminated soil and evaluated for its degradation efficiency and potential use against QS-mediated pathogens. Strain XN-10 could effectively degrade N-(3-oxohexanoyl)-L-homoserine lactone (OHHL), N-hexanoyl-L-homoserine lactone (C6HSL), N-(3-oxododecanoyl)-L-homoserine lactone (3OC12HSL), and N-(3-oxooctanoyl)-L-homoserine lactone (3OC8HSL), which all belong to the AHL family. Analysis of AHL metabolic products by gas chromatography–mass spectrometry (GC-MS) led to the identification of N-cyclohexyl-propanamide, and pentanoic acid, 4-methyl, methyl ester as the main intermediate metabolites, revealing that AHL could be degraded by hydrolysis and dehydroxylation. All intermediates were transitory and faded away without any non-cleavable metabolites at the end of the experiment. Furthermore, strain XN-10 significantly attenuated the pathogenicity of Pectobacterium carotovorum subsp. carotovorum (Pcc) to suppress tissue maceration in carrots, potatoes, and Chinese cabbage. Taken together, our results shed light on the QQ mechanism of a novel AHL-degrading bacterial isolate, and they provide useful information which show potential for biocontrol of infectious diseases caused by AHL-dependent bacterial pathogens.

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Section: Discussionmentioning

confidence: 99%

“…It is widely accepted that resistance is less likely to develop, because QQ strains impart less selective pressures. However, resistance attributes to QS inhibitors have already been discovered in laboratory and clinical settings [ 25 , 52 ]. Therefore, it is a considerable and notable phenomenon.…”

Section: Discussionmentioning

confidence: 99%

Quorum Quenching in a Novel Acinetobacter sp. XN-10 Bacterial Strain against Pectobacterium carotovorum subsp. carotovorum

et al. 2020

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“…Antivirulence therapies. The 33 antivirulence projects that we identified are pursuing a wide range of strategies, including inhibition of quorum sensing, biofilm formation, adhesion, diverse regulators and persisters [67][68][69][70][71] . Antivirulence drugs need to be combined with a direct-acting antibacterial therapeutic and are designed as adjunctive therapies.…”

Section: Compassionate Usementioning

confidence: 99%

The global preclinical antibacterial pipeline

Theuretzbacher¹,

et al. 2019

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| Antibacterial resistance is a great concern and requires global action. A critical question is whether enough new antibacterial drugs are being discovered and developed. A review of the clinical antibacterial drug pipeline was recently published, but comprehensive information about the global preclinical pipeline is unavailable. This Review focuses on discovery and preclinical development projects and has found, as of 1 May 2019, 407 antibacterial projects from 314 institutions. The focus is on Gram-negative pathogens, particularly bacteria on the WHO priority bacteria list. The preclinical pipeline is characterized by high levels of diversity and interesting scientific concepts, with 135 projects on direct-acting small molecules that represent new classes, new targets or new mechanisms of action. There is also a strong trend towards non-traditional approaches, including diverse antivirulence approaches, microbiome-modifying strategies, and engineered phages and probiotics. The high number of pathogen-specific and adjunctive approaches is unprecedented in antibiotic history. Translational hurdles are not adequately addressed yet, especially development pathways to show clinical impact of nontraditional approaches. The innovative potential of the preclinical pipeline compared with the clinical pipeline is encouraging but fragile. Much more work , focus and funding are needed for the novel approaches to result in effective antibacterial therapies to sustainably combat antibacterial resistance.

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“…the use of a quorum-quenching enzyme to disrupt bacterial communication, leading to the inhibition of biofilm formation. 17) With the number of phages already sequenced, and the techniques available to improve enzyme function [18][19][20] and phage manipulation, these approaches could constitute a useful weapon to incorporate into future strategies.…”

Section: Engineering Host Specificitiesmentioning

confidence: 99%

Engineered Bacteriophages for Practical Applications

Pizarro-Bäuerle

Ando

2020

Biological & Pharmaceutical Bulletin

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The diversity of advanced genetic engineering techniques that have become available in recent years has enabled a more precise manipulation of genes and genomes. Among these, bacteriophage genomes stand out as an interesting target due to their dependence on a host for replication, which previously complicated their manipulation, and due as well to the many possible fields in which they can be used. In this review, we highlight recent applications for which genetically modified bacteriophages are being employed: as phage therapy in medicine, animal industries and agricultural settings; as a source of new antimicrobials; as biosensors for research, health and environmental purposes; and as genetic engineering tools themselves.

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Engineering quorum quenching enzymes: progress and perspectives

Cited by 51 publications

References 61 publications

Quorum Quenching in a Novel Acinetobacter sp. XN-10 Bacterial Strain against Pectobacterium carotovorum subsp. carotovorum

Quorum Quenching in a Novel Acinetobacter sp. XN-10 Bacterial Strain against Pectobacterium carotovorum subsp. carotovorum

The global preclinical antibacterial pipeline

Engineered Bacteriophages for Practical Applications

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