Impact of the structure-activity relationship of AHL analogues on quorum sensing in Gram-negative bacteria

Chbib, Christiane

doi:10.1016/j.bmc.2019.115282

Cited by 17 publications

(8 citation statements)

References 35 publications

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“…Once a critical cell density threshold is reached, these signals interact with their cognate receptors and coordinate the expression of associated genes [ 4 ]. In Gram-positive and Gram-negative bacteria, several QS systems have been identified [ 5 , 6 ], including acyl-homoserine lactone (AHL)-based and peptide-based QS systems. In addition, many proteobacteria use the AHL-dependent QS system to regulate population-dependent behaviors, including plasmid conjugation, pigment production, virulence factor expression, and biofilm formation [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Molecular Mechanisms and Applications of N-Acyl Homoserine Lactone-Mediated Quorum Sensing in Bacteria

et al. 2022

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Microbial biodiversity includes biotic and abiotic components that support all life forms by adapting to environmental conditions. Climate change, pollution, human activity, and natural calamities affect microbial biodiversity. Microbes have diverse growth conditions, physiology, and metabolism. Bacteria use signaling systems such as quorum sensing (QS) to regulate cellular interactions via small chemical signaling molecules which also help with adaptation under undesirable survival conditions. Proteobacteria use acyl-homoserine lactone (AHL) molecules as autoinducers to sense population density and modulate gene expression. The LuxI-type enzymes synthesize AHL molecules, while the LuxR-type proteins (AHL transcriptional regulators) bind to AHLs to regulate QS-dependent gene expression. Diverse AHLs have been identified, and the diversity extends to AHL synthases and AHL receptors. This review comprehensively explains the molecular diversity of AHL signaling components of Pseudomonas aeruginosa, Chromobacterium violaceum, Agrobacterium tumefaciens, and Escherichia coli. The regulatory mechanism of AHL signaling is also highlighted in this review, which adds to the current understanding of AHL signaling in Gram-negative bacteria. We summarize molecular diversity among well-studied QS systems and recent advances in the role of QS proteins in bacterial cellular signaling pathways. This review describes AHL-dependent QS details in bacteria that can be employed to understand their features, improve environmental adaptation, and develop broad biomolecule-based biotechnological applications.

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Section: Introductionmentioning

confidence: 99%

Molecular Mechanisms and Applications of N-Acyl Homoserine Lactone-Mediated Quorum Sensing in Bacteria

et al. 2022

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“…Numerous QQ agents have been identified that inhibit key QS pathways, AHL synthesis or AHL receptors in P. aeruginosa and other bacteria. However, the majority of QQ drugs remain in pre-clinical stages with some repurposed drugs in clinical trials (Figure 1) (18).…”

Section: Toxin-binding Monoclonal Antibodiesmentioning

confidence: 99%

Microbial Genomics as a Catalyst for Targeted Antivirulence Therapeutics

Sintchenko

Timms

E³

et al. 2021

Front. Med.

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Virulence arresting drugs (VAD) are an expanding class of antimicrobial treatment that act to “disarm” rather than kill bacteria. Despite an increasing number of VAD being registered for clinical use, uptake is hampered by the lack of methods that can identify patients who are most likely to benefit from these new agents. The application of pathogen genomics can facilitate the rational utilization of advanced therapeutics for infectious diseases. The development of genomic assessment of VAD targets is essential to support the early stages of VAD diffusion into infectious disease management. Genomic identification and characterization of VAD targets in clinical isolates can augment antimicrobial stewardship and pharmacovigilance. Personalized genomics guided use of VAD will provide crucial policy guidance to regulating agencies, assist hospitals to optimize the use of these expensive medicines and create market opportunities for biotech companies and diagnostic laboratories.

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“…However, P. aeruginosa regulates the production of a variety of virulence factors and biofilms through the las , rhl , pqs , and iqs QS systems, which destroys tissues and induces inflammation, leading to impaired immune mechanisms, in an infected patient ( Van Delden and Iglewski, 1998 ). Therefore, studies in P. aeruginosa have focused on QSIs that target QS mediated by acyl-homoserine lactone (AHL) signaling molecules ( Chbib, 2020 ; Jiang et al, 2020 ). Nevertheless, P. aeruginosa can sense the AI-2 signaling molecule produced by other bacteria, such as Escherichia coli ( Roy et al, 2011 ), Salmonella typhimurium ( Roy et al, 2011 ), Streptococcus mitis ( Wang et al, 2016b ), and S. aureus ( Hotterbeekx et al, 2017 ), which regulates the production of virulence factors and biofilms and increases its pathogenicity ( Li et al, 2015 ; Wang et al, 2016b ).…”

Section: Introductionmentioning

confidence: 99%

Effect of Autoinducer-2 Quorum Sensing Inhibitor on Interspecies Quorum Sensing

Jiang

Xu²,

Yuan

et al. 2022

Front. Microbiol.

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Bacterial drug resistance caused by overuse and misuse of antibiotics is common, especially in clinical multispecies infections. It is of great significance to discover novel agents to treat clinical bacterial infections. Studies have demonstrated that autoinducer-2 (AI-2), a signal molecule in quorum sensing (QS), plays an important role in communication among multiple bacterial species and bacterial drug-resistance. Previously, 14 AI-2 inhibited compounds were selected through virtual screening by using the AI-2 receptor protein LuxP as a target. Here, we used Vibrio harveyi BB170 as a reporter strain for the preliminary screening of 14 inhibitors and compound Str7410 had higher AI-2 QS inhibition activity (IC50 = 0.3724 ± 0.1091 μM). Then, co-culture of Pseudomonas aeruginosa PAO1 with Staphylococcus aureus ATCC 25923 was used to evaluate the inhibitory effects of Str7410 on multispecies infection in vitro and in vivo. In vitro, Str7410 significantly inhibited the formation of mixed bacterial biofilms. Meanwhile, the combination of Str7410 with meropenem trihydrate (MEPM) significantly improved the susceptibility of mixed-species-biofilm cells to the antibiotic. In vivo, Str7410 significantly increased the survival rate of wild-type Caenorhabditis elegans N2 co-infected by P. aeruginosa PAO1 and S. aureus ATCC 25923. Real-time quantitative PCR analysis showed that Str7410 reduced virulence factor (pyocyanin and elastase) production and swarming motility of P. aeruginosa PAO1 by downregulating the expression of QS-related genes in strain PAO1 in co-culture with S. aureus ATCC 25923. Compound Str7410 is a candidate agent for treating drug-resistant multispecies infections. The work described here provides a strategy for discovering novel antibacterial drugs.

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Impact of the structure-activity relationship of AHL analogues on quorum sensing in Gram-negative bacteria

Cited by 17 publications

References 35 publications

Molecular Mechanisms and Applications of N-Acyl Homoserine Lactone-Mediated Quorum Sensing in Bacteria

Molecular Mechanisms and Applications of N-Acyl Homoserine Lactone-Mediated Quorum Sensing in Bacteria

Microbial Genomics as a Catalyst for Targeted Antivirulence Therapeutics

Effect of Autoinducer-2 Quorum Sensing Inhibitor on Interspecies Quorum Sensing

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