Saline Environments as a Source of Potential Quorum Sensing Disruptors to Control Bacterial Infections: A Review

Saline environments, such as marine and hypersaline habitats, are widely distributed around the world. They include sea waters, saline lakes, solar salterns, or hypersaline soils. The bacteria that live in these habitats produce and develop unique bioactive molecules and physiological pathways to cope with the stress conditions generated by these environments. They have been described to produce compounds with properties that differ from those found in non-saline habitats. In the last decades, the ability to disrupt quorum-sensing (QS) intercellular communication systems has been identified in many marine organisms, including bacteria. The two main mechanisms of QS interference, i.e., quorum sensing inhibition (QSI) and quorum quenching (QQ), appear to be a more frequent phenomenon in marine aquatic environments than in soils. However, data concerning bacteria from hypersaline habitats is scarce. Salt-tolerant QSI compounds and QQ enzymes may be of interest to interfere with QS-regulated bacterial functions, including virulence, in sectors such as aquaculture or agriculture where salinity is a serious environmental issue. This review provides a global overview of the main works related to QS interruption in saline environments as well as the derived biotechnological applications.

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Bacillus spp. Inhibit Edwardsiella tarda Quorum-Sensing and Fish Infection

Marine Drugs ◽

10.3390/md19110602 ◽

2021 ◽

Vol 19 (11) ◽

pp. 602

Author(s):

Rafaela A. Santos ◽

Marta Monteiro ◽

Fábio Rangel ◽

Russell Jerusik ◽

Maria J. Saavedra ◽

...

Keyword(s):

Quorum Sensing ◽

Bacterial Infections ◽

Quorum Quenching ◽

Bioactive Molecules ◽

Edwardsiella Tarda ◽

Fish Pathogens ◽

Bacillus Spp ◽

Photobacterium Damselae ◽

Health Promoting ◽

Promising Source

The disruption of pathogen communication or quorum-sensing (QS) via quorum-quenching (QQ) molecules has been proposed as a promising strategy to fight bacterial infections. Bacillus spp. have recognizable biotechnology applications, namely as probiotic health-promoting agents or as a source of natural antimicrobial molecules, including QQ molecules. This study characterized the QQ potential of 200 Bacillus spp., isolated from the gut of different aquaculture fish species, to suppress fish pathogens QS. Approximately 12% of the tested Bacillus spp. fish isolates (FI). were able to interfere with synthetic QS molecules. Ten isolates were further selected as producers of extracellular QQ-molecules and their QQ capacity was evaluated against the QS of important aquaculture bacterial pathogens, namely Aeromonas spp., Vibrio spp., Photobacterium damselae, Edwardsiela tarda, and Shigella sonnei. The results revealed that A. veronii and E. tarda produce QS molecules that are detectable by the Chr. violaceum biosensor, and which were degraded when exposed to the extracellular extracts of three FI isolates. Moreover, the same isolates, identified as B. subtilis, B. vezelensis, and B. pumilus, significantly reduced the pathogenicity of E. tarda in zebrafish larvae, increasing its survival by 50%. Taken together, these results identified three Bacillus spp. capable of extracellularly quenching aquaculture pathogen communication, and thus become a promising source of bioactive molecules for use in the biocontrol of aquaculture bacterial diseases.

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Inhibición del quórum sensing mediante el quórum quenching en postlarvas de Litopenaeus vannamei

La Técnica: Revista de las Agrociencias. ISSN 2477-8982 ◽

10.33936/la_tecnica.v0i23.1538 ◽

2020 ◽

pp. 01

Author(s):

Jefferson Javier Intriago Angulo ◽

Juan Gerardo Quimi Mujica ◽

Jordana Jineyka López Parra ◽

David Villarreal de la Torre ◽

Edmundo Matute ◽

...

Keyword(s):

Quorum Sensing ◽

Litopenaeus Vannamei ◽

Bacterial Infections ◽

Pathogenic Bacteria ◽

Survival Rates ◽

Quorum Quenching ◽

Probiotic Bacteria ◽

White Shrimp ◽

In Vitro Tests

Inhibition of the quorum sensing by quorum quenching in postlarva of Litopenaeus vannamei El cultivo del camarón blanco Litopenaeus vannamei es un recurso acuícola de gran importancia económica a nivel mundial; sin embargo, es severamente afectado por varios tipos de enfermedades infecciosas, principalmente virales y bacterianas. Sin embargo las pérdidas masivas reportadas durante los últimos años, están generalmente relacionadas a infecciones bacterianas en particular, el síndrome de mortalidad temprana (EMS) y más recientemente relacionada a la enfermedad de necrosis hepatopancreática aguda (AHPND) por sus siglas en ingles. Para asegurar la sostenibilidad de la industria del camarón, se debe mejorar la productividad en particular mediante el uso de consorcios de bacterias probióticas eficientes para la prevención de las enfermedades bacterianas. Dos consorcios de bacterias probióticas (consorcios comerciales y consorcio CA), fueron evaluados en pruebas in vitro y en tanques de producción de post-larvas de camarón L. vannamei, donde se realizó la determinación subsecuente del grado de inhibición del quórum sensing de las bacterias patogénicas mediante el quórum quenching de bacterias probióticas y paralelamente a los análisis de sobrevivencia. Como resultados el consorcio CA fue el que presento mayor grado de inhibición del quorum sensing in vitro en paralelo a los mayores porcentajes de sobrevivencia en tanques de producción de post-larvas de camarón. El mejor efecto probiótico en post-larvas de L. vannamei resultaron en los tratamientos del consorcio CA, como los mejores supresores en la presencia de vibrios en el cultivo bacteriológico así como mayores porcentajes de sobrevivencia en tanques de producción de post-larvas de camarón. Palabras clave: Litopenaeus vannamei; quorum sensing; quorum quenching; bacterias patogénicas; bacterias probióticas Abstract The cultivation of white shrimp Litopenaeus vannamei is an aquaculture resource of great economic importance worldwide; however, it is severely affected by several types of infectious diseases, mainly viral and bacterial. However, the massive losses reported in recent years are generally related to bacterial infections in particular, early mortality syndrome (EMS) and more recently related to acute hepatopancreatic necrosis disease (AHPND). To ensure the sustainability of the shrimp industry, productivity must be improved in particular by the use of efficient probiotic bacteria consortia for the prevention of bacterial diseases. Two consortia of probiotic bacteria (commercial consortia and CA consortium) were evaluated in in vitro tests and in post-larvae production tanks of L. vannamei shrimp, where the subsequent determination of the degree of inhibition of the quorum sensing of pathogenic bacteria was carried out. By the quenching quorum of probiotic bacteria and parallel to the survival analysis. As a result, the CA consortium showed the greatest degree of inhibition of in vitro quorum sensing in parallel to the higher survival rates in shrimp post-larval production tanks. The best probiotic effect in post-larvae of L. vannamei resulted in the CA consortia treatments, as the best suppressors in the presence of vibrios in the bacteriological culture as well as higher survival rates in post-larvae shrimp production tanks Keywords: Litopenaeus vannamei; quorum sensing; quorum quenching; pathogenic bacteria; probiotic bacteria.

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Quorum Sensing Pseudomonas Quinolone Signal Forms Chiral Supramolecular Assemblies With the Host Defense Peptide LL-37

Frontiers in Molecular Biosciences ◽

10.3389/fmolb.2021.742023 ◽

2021 ◽

Vol 8 ◽

Author(s):

Ferenc Zsila ◽

Maria Ricci ◽

Imola Csilla Szigyártó ◽

Priyanka Singh ◽

Tamás Beke-Somfai

Keyword(s):

Quorum Sensing ◽

Host Defense ◽

Bacterial Infections ◽

Molecular Mechanisms ◽

Cell Communication ◽

Quorum Quenching ◽

Bacterial Biofilms ◽

Phenotypic Traits ◽

Signal Molecules ◽

Supramolecular Architectures

Host defense antimicrobial peptides (HDPs) constitute an integral component of the innate immune system having nonspecific activity against a broad spectrum of microorganisms. They also have diverse biological functions in wound healing, angiogenesis, and immunomodulation, where it has also been demonstrated that they have a high affinity to interact with human lipid signaling molecules. Within bacterial biofilms, quorum sensing (QS), the vital bacterial cell-to-cell communication system, is maintained by similar diffusible small molecules which control phenotypic traits, virulence factors, biofilm formation, and dispersion. Efficient eradication of bacterial biofilms is of particular importance as these colonies greatly help individual cells to tolerate antibiotics and develop antimicrobial resistance. Regarding the antibacterial function, for several HDPs, including the human cathelicidin LL-37, affinity to eradicate biofilms can exceed their activity to kill individual bacteria. However, related underlying molecular mechanisms have not been explored yet. Here, we employed circular dichroism (CD) and UV/VIS spectroscopic analysis, which revealed that LL-37 exhibits QS signal affinity. This archetypal representative of HDPs interacts with the Pseudomonas quinolone signal (PQS) molecules, producing co-assemblies with peculiar optical activity. The binding of PQS onto the asymmetric peptide chains results in chiral supramolecular architectures consisting of helically disposed, J-aggregated molecules. Besides the well-known bacterial membrane disruption activity, our data propose a novel action mechanism of LL-37. As a specific case of the so-called quorum quenching, QS signal molecules captured by the peptide are sequestered inside co-assemblies, which may interfere with the microbial QS network helping to prevent and eradicate bacterial infections.

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Acinetobacter baumannii Quorum sensing: A way to communicate and a target to eradicate

International Journal of Science and Research Archive ◽

10.30574/ijsra.2021.3.2.0112 ◽

2021 ◽

Vol 3 (2) ◽

pp. 134-145

Author(s):

Elkheloui Raja ◽

Hamadi Fatima ◽

Mimouni Rachida

Keyword(s):

Quorum Sensing ◽

Acinetobacter Baumannii ◽

Virulence Factors ◽

Bacterial Infections ◽

Quorum Quenching ◽

Signal Molecules ◽

Gram Negative Bacteria ◽

Chronic Infections ◽

New Strategy

Quorum sensing is a communication system based on the actions of chemical signal molecules depending on the density of the cell population. These molecules are widely considered as effectors of the gene expression of several virulence factors. As a result, it has attracted a lot of attention because of its possible applicability as a target for treating infections. This review attempts to give a description of this system on gram negative bacteria specifically on Acinetobacter baumannii as an important nosocomial pathogen. Additionally, quorum sensing in biofilm will be also treated because it is considered as the origin of several chronic infections. Numerous studies have been carried out to prove the role of inhibitors in the disruption of quorum sensing, known as quorum quenching. Quorum quenching is a new strategy to eradicate bacterial infections due to the crucial intervention of quorum sensing in different virulence factors and particularly in the biofilm formation.

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Peptide signaling without feedback in signal production operates as a true quorum sensing communication system in Bacillus subtilis

Communications Biology ◽

10.1038/s42003-020-01553-5 ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Iztok Dogsa ◽

Mihael Spacapan ◽

Anna Dragoš ◽

Tjaša Danevčič ◽

Žiga Pandur ◽

...

Keyword(s):

Gene Expression ◽

Bacillus Subtilis ◽

Quorum Sensing ◽

Cell Density ◽

Communication System ◽

Communication Systems ◽

Feedback Loop ◽

Signal Molecules ◽

Specific Cell ◽

Sharp Transition

AbstractBacterial quorum sensing (QS) is based on signal molecules (SM), which increase in concentration with cell density. At critical SM concentration, a variety of adaptive genes sharply change their expression from basic level to maximum level. In general, this sharp transition, a hallmark of true QS, requires an SM dependent positive feedback loop, where SM enhances its own production. Some communication systems, like the peptide SM-based ComQXPA communication system of Bacillus subtilis, do not have this feedback loop and we do not understand how and if the sharp transition in gene expression is achieved. Based on experiments and mathematical modeling, we observed that the SM peptide ComX encodes the information about cell density, specific cell growth rate, and even oxygen concentration, which ensure power-law increase in SM production. This enables together with the cooperative response to SM (ComX) a sharp transition in gene expression level and this without the SM dependent feedback loop. Due to its ultra-sensitive nature, the ComQXPA can operate at SM concentrations that are 100–1000 times lower than typically found in other QS systems, thereby substantially reducing the total metabolic cost of otherwise expensive ComX peptide.

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Cross-kingdom inhibition of bacterial virulence and communication by probiotic yeast metabolites

Microbiome ◽

10.1186/s40168-021-01027-8 ◽

2021 ◽

Vol 9 (1) ◽

Author(s):

Orit Malka ◽

Dorin Kalson ◽

Karin Yaniv ◽

Reut Shafir ◽

Manikandan Rajendran ◽

...

Keyword(s):

Quorum Sensing ◽

Gut Microbiome ◽

Bacterial Infections ◽

Pathogenic Bacteria ◽

Molecular Mechanisms ◽

Human Microbiome ◽

Cell Communication ◽

Probiotic Yeast ◽

Gut Pathogen ◽

Cell Cell

Abstract Background Probiotic milk-fermented microorganism mixtures (e.g., yogurt, kefir) are perceived as contributing to human health, and possibly capable of protecting against bacterial infections. Co-existence of probiotic microorganisms are likely maintained via complex biomolecular mechanisms, secreted metabolites mediating cell-cell communication, and other yet-unknown biochemical pathways. In particular, deciphering molecular mechanisms by which probiotic microorganisms inhibit proliferation of pathogenic bacteria would be highly important for understanding both the potential benefits of probiotic foods as well as maintenance of healthy gut microbiome. Results The microbiome of a unique milk-fermented microorganism mixture was determined, revealing a predominance of the fungus Kluyveromyces marxianus. We further identified a new fungus-secreted metabolite—tryptophol acetate—which inhibits bacterial communication and virulence. We discovered that tryptophol acetate blocks quorum sensing (QS) of several Gram-negative bacteria, particularly Vibrio cholerae, a prominent gut pathogen. Notably, this is the first report of tryptophol acetate production by a yeast and role of the molecule as a signaling agent. Furthermore, mechanisms underscoring the anti-QS and anti-virulence activities of tryptophol acetate were elucidated, specifically down- or upregulation of distinct genes associated with V. cholerae QS and virulence pathways. Conclusions This study illuminates a yet-unrecognized mechanism for cross-kingdom inhibition of pathogenic bacteria cell-cell communication in a probiotic microorganism mixture. A newly identified fungus-secreted molecule—tryptophol acetate—was shown to disrupt quorum sensing pathways of the human gut pathogen V. cholerae. Cross-kingdom interference in quorum sensing may play important roles in enabling microorganism co-existence in multi-population environments, such as probiotic foods and the gut microbiome. This discovery may account for anti-virulence properties of the human microbiome and could aid elucidating health benefits of probiotic products against bacterially associated diseases.

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Identification of New Potential Inhibitors of Quorum Sensing through a Specialized Multi-Level Computational Approach

Molecules ◽

10.3390/molecules26092600 ◽

2021 ◽

Vol 26 (9) ◽

pp. 2600

Author(s):

Fábio G. Martins ◽

André Melo ◽

Sérgio F. Sousa

Keyword(s):

Virtual Screening ◽

Quorum Sensing ◽

In Silico ◽

Bacterial Infections ◽

Extracellular Polymeric Substances ◽

Free Energy Calculations ◽

Ligand Docking ◽

Screening Tests ◽

Scoring Functions ◽

Potential Inhibitors

Biofilms are aggregates of microorganisms anchored to a surface and embedded in a self-produced matrix of extracellular polymeric substances and have been associated with 80% of all bacterial infections in humans. Because bacteria in biofilms are less amenable to antibiotic treatment, biofilms have been associated with developing antibiotic resistance, a problem that urges developing new therapeutic options and approaches. Interfering with quorum-sensing (QS), an important process of cell-to-cell communication by bacteria in biofilms is a promising strategy to inhibit biofilm formation and development. Here we describe and apply an in silico computational protocol for identifying novel potential inhibitors of quorum-sensing, using CviR—the quorum-sensing receptor from Chromobacterium violaceum—as a model target. This in silico approach combines protein-ligand docking (with 7 different docking programs/scoring functions), receptor-based virtual screening, molecular dynamic simulations, and free energy calculations. Particular emphasis was dedicated to optimizing the discrimination ability between active/inactive molecules in virtual screening tests using a target-specific training set. Overall, the optimized protocol was used to evaluate 66,461 molecules, including those on the ZINC/FDA-Approved database and to the Mu.Ta.Lig Virtual Chemotheca. Multiple promising compounds were identified, yielding good prospects for future experimental validation and for drug repurposing towards QS inhibition.

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