Quenching bacterial communication in order to decrease their virulence and increase their sensitivity to antimicrobial treatments

De nombreuses bactéries utilisent un système de communication moléculaire, le Quorum Sensing (QS), afin de synchroniser leur comportement en fonction de la densité de population. Le QS régule l’expression de gènes associés à la virulence, la formation de biofilm, la résistance aux antimicrobiens ou la compétition inter-espèces. Bloquer le QS, une stratégie appelée Quorum Quenching (QQ) est prometteuse pour diminuer la virulence bactérienne et augmenter l’efficacité des antibiotiques ou autres bactériophages. L’enzyme SsoPox, capable de bloquer le QS de bactéries à Gram négatif, a été étudiée ainsi que sa complémentarité avec des traitements antibactériens. L’enzyme s’est montrée capable de diminuer la virulence et la formation de biofilm chez des souches modèles et des isolats cliniques de Pseudomonas aeruginosa multirésistants. Des effets synergiques avec la ciprofloxacine et un cocktail de bactériophages ont par ailleurs mis en évidence sa capacité à augmenter la sensibilité des bactéries aux antimicrobiens. L’impact de SsoPox sur un mécanisme de résistance bactérien, le système CRISPR-Cas, a ensuite été démontré et permettrait de limiter le développement de résistances aux bactériophages. Enfin, l’utilisation d’une approche combinant protéomique et métabolomique a permis d’étudier l’impact de SsoPox sur une bactérie environnementale Chromobacterium violaceum et de montrer son potentiel pour modifier la compétition de la bactérie envers d’autres organismes procaryotes et eucaryotes. Ainsi tous ces travaux tendent à montrer que SsoPox serait efficace comme complément voire alternative aux antimicrobiens et pourrait également être utilisée pour modifier des microbiotesMany bacteria use a molecular communication system, referred to as Quorum Sensing (QS), to synchronize their behavior in a cell density-dependent manner. QS regulates the expression of genes involved in virulence, biofilm formation, antimicrobial resistance or interspecies competition. Disrupting QS, a strategy called Quorum Quenching (QQ) is a promising way to inhibit bacterial virulence and increase antibiotic or bacteriophage efficiency. SsoPox, an enzyme able to quench QS of gram-negative bacteria, was studied along with its complementarity with antibacterial treatments. The enzyme successfully decreased virulence and biofilm formation in multi-resistant model strain and clinical isolates of Pseudomonas aeruginosa. Synergetic effects with ciprofloxacin and a bacteriophage cocktail highlighted its capacity to enhance bacterial sensitivity to antimicrobials. SsoPox impact on a bacterial resistance mechanism, namely the CRISPR-Cas system, was then shown and could limit the development of resistance to bacteriophages. Finally, an approach combining proteomic and metabolomic analyses was used to investigate SsoPox impact on an environmental bacteria, Chromobacterium violaceum and was shown to alter its capacity to compete with prokaryotic and eukaryotic organisms. Thus, all this work suggests that SsoPox would be an efficient complement or even an alternative to antimicrobials and could also be used to modulate microbiota

: Comment bloquer la communication des bactéries pour inhiber leur virulence ?

La plupart des bactéries utilisent un système de communication, le quorum sensing, fondé sur la sécrétion et la perception de petites molécules appelées autoinducteurs qui leur permettent d’adapter leur comportement en fonction de la taille de la population. Les bactéries mutualisent ainsi leurs efforts de survie en synchronisant entre elles la régulation de gènes impliqués notamment dans la virulence, la résistance aux antimicrobiens ou la formation du biofilm. Des méthodes ont vu le jour pour inhiber cette communication entre bactéries et limiter leurs effets nocifs. Des inhibiteurs chimiques, des anticorps ou encore des enzymes capables d’interférer avec les autoinducteurs ont été développés et se sont montrés efficaces pour diminuer la virulence des bactéries à la fois in vitro et in vivo. Cette stratégie, appelée quorum quenching, a également montré des effets synergiques avec des traitements antibactériens classiques. Il permettrait notamment d’augmenter la sensibilité des bactéries aux antibiotiques. Ceci constitue une piste thérapeutique prometteuse pour lutter contre les infections bactériennes et limiter les conséquences de l’antibiorésistance

Lactonase SsoPox modulates CRISPR-Cas expression in gram-negative proteobacteria using AHL-based quorum sensing systems

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Quorum sensing et quorum quenching : Comment bloquer la communication des bactéries pour inhiber leur virulence ?

International audienceMost bacteria use a communication system known as quorum sensing which relies on the secretion and perception of small molecules called autoinducers enabling bacteria to adapt their behavior according to the population size and synchronize the expression of genes involved in virulence, antimicrobial resistance and biofilm formation. Methods have emerged to inhibit bacterial communication and limit their noxious traits. Chemical inhibitors, sequestering antibodies and degrading enzymes have been developed and proved efficient to decrease bacterial virulence both in vitro and in vivo. This strategy, named quorum quenching, also showed synergistic effects with traditional antibacterial treatments by increasing bacterial susceptibility to antibiotics. Thereby quorum quenching constitutes an interesting therapeutic strategy to fight against bacterial infections and limit the consequences of antibiotic resistance.La plupart des bactéries utilisent un système de communication, le quorum sensing, fondé sur la sécrétion et la perception de petites molécules appelées autoinducteurs qui leur permettent d’adapter leur comportement en fonction de la taille de la population. Les bactéries mutualisent ainsi leurs efforts de survie en synchronisant entre elles la régulation de gènes impliqués notamment dans la virulence, la résistance aux antimicrobiens ou la formation du biofilm. Des méthodes ont vu le jour pour inhiber cette communication entre bactéries et limiter leurs effets nocifs. Des inhibiteurs chimiques, des anticorps ou encore des enzymes capables d’interférer avec les autoinducteurs ont été développés et se sont montrés efficaces pour diminuer la virulence des bactéries à la fois in vitro et in vivo. Cette stratégie, appelée quorum quenching, a également montré des effets synergiques avec des traitements antibactériens classiques. Il permettrait notamment d’augmenter la sensibilité des bactéries aux antibiotiques. Ceci constitue une piste thérapeutique prometteuse pour lutter contre les infections bactériennes et limiter les conséquences de l’antibiorésistance

Quorum Quenching Lactonase Strengthens Bacteriophage and Antibiotic Arsenal Against Pseudomonas aeruginosa Clinical Isolates

International audienceMany bacteria use quorum sensing (QS), a bacterial communication system based on the diffusion and perception of small signaling molecules, to synchronize their behavior in a cell-density dependent manner. QS regulates the expression of many genes associated with virulence factor production and biofilm formation. This latter is known to be involved in antibiotic and phage resistance mechanisms. Therefore, disrupting QS, a strategy known as quorum quenching (QQ), appears to be an interesting way to reduce bacterial virulence and increase antibiotic and phage treatment efficiency. In this study, the ability of the QQ enzyme SsoPox-W263I, a lactonase able to degrade acyl-homoserine lactones, was investigated for quenching both virulence and biofilm formation in clinical isolates of Pseudomonas aeruginosa from diabetic foot ulcers, as well as in the PA14 model strain. These strains were further evolved to resist to bacteriophage cocktails. Overall, 10 antibiotics or bacteriophage resistant strains were evaluated and SsoPox-W263I was shown to decrease pyocyanin, protease and elastase production in all strains. Furthermore, a reduction of more than 70% of biofilm formation was achieved in six out of ten strains. This anti-virulence potential was confirmed in vivo using an amoeba infection model, showing enhanced susceptibility toward amoeba of nine out of ten P. aeruginosa isolates upon QQ. This amoeba model was further used to demonstrate the ability of SsoPox-W263I to enhance the susceptibility of sensitive and phage resistant bacteria to bacteriophage and antibiotic

Interference in Bacterial Quorum Sensing: A Biopharmaceutical Perspective

Numerous bacteria utilize molecular communication systems referred to as quorum sensing (QS) to synchronize the expression of certain genes regulating, among other aspects, the expression of virulence factors and the synthesis of biofilm. To achieve this process, bacteria use signaling molecules, known as autoinducers (AIs), as chemical messengers to share information. Naturally occurring strategies that interfere with bacterial signaling have been extensively studied in recent years, examining their potential to control bacteria. To interfere with QS, bacteria use quorum sensing inhibitors (QSIs) to block the action of AIs and quorum quenching (QQ) enzymes to degrade signaling molecules. Recent studies have shown that these strategies are promising routes to decrease bacterial pathogenicity and decrease biofilms, potentially enhancing bacterial susceptibility to antimicrobial agents including antibiotics and bacteriophages. The efficacy of QSIs and QQ enzymes has been demonstrated in various animal models and are now considered in the development of new medical devices against bacterial infections, including dressings, and catheters for enlarging the therapeutic arsenal against bacteria

Disrupting quorum sensing alters social interactions in Chromobacterium violaceum

International audienceQuorum sensing (QS) is a communication system used by bacteria to coordinate a wide panel of biological functions in a cell density-dependent manner. The Gram-negative Chromobacterium violaceum has previously been shown to use an acyl-homoserine lactone (AHL)-based QS to regulate various behaviors, including the production of proteases, hydrogen cyanide, or antimicrobial compounds such as violacein. By using combined metabolomic and proteomic approaches, we demonstrated that QS modulates the production of antimicrobial and toxic compounds in C. violaceum ATCC 12472. We provided the first evidence of anisomycin antibiotic production by this strain as well as evidence of its regulation by QS and identified new AHLs produced by C. violaceum ATCC 12472. Furthermore, we demonstrated that targeting AHLs with lactonase leads to major QS disruption yielding significant molecular and phenotypic changes. These modifications resulted in drastic changes in social interactions between C. violaceum and a Gram-positive bacterium ( Bacillus cereus ), a yeast ( Saccharomyces cerevisiae ), immune cells (murine macrophages), and an animal model (planarian Schmidtea mediterranea ). These results underscored that AHL-based QS plays a key role in the capacity of C. violaceum to interact with micro- and macroorganisms and that quorum quenching can affect microbial population dynamics beyond AHL-producing bacteria and Gram-negative bacteria

Swallowable obalon® gastric balloons as an aid for weight loss: A pilot feasibility study

The goal of this study was to evaluate the safety and the impact on weight loss of a new swallowable gastric balloon. In this prospective pilot study, 17 overweight or obese patients were included. Up to three balloons were ingested under fluoroscopic control. All balloons were removed by upper GI endoscopy, 12 weeks after the ingestion of the first balloon. 43 out of 44 attempts (98 %) to swallow a balloon were successful. Nausea and stomach pain were the most frequent side effects. Endoscopic procedures for balloon removal were uneventful. Weight loss was significant at weeks 4, 8, and 12. This pilot study showed no significant side effects induced by up to three balloons, and a significant weight loss. © 2013 Springer Science+Business Media New York.SCOPUS: ar.jinfo:eu-repo/semantics/publishe