RESUMEN
Autoinducer-2 (AI-2)-mediated quorum sensing (QS) is utilised for both intra- and inter-species communication by a wide variety of bacteria. An understanding of the mechanism of this communication has the potential to elucidate new targets for antibacterial therapeutics. Herein, we report the synthesis of DPD analogues with modified dynamic equilibria and the evaluation of their behaviour in Gram-negative bacteria. None of the compounds showed modulation of QS in S. Typhimurium, and although no antagonism of V. harveyi was observed, chloro-analogue C5-Cl-DPD showed modest agonism in this marine bacterium. This raises the possibility that access to a cyclic form of DPD may not be required for AI-2-mediated QS in V. harveyi.
RESUMEN
Botulinum neurotoxicity is characterized by peripheral neuromuscular blockade/flaccid paralysis that can lead to respiratory failure and ultimately death. Current therapeutic options provide relief in a pre-exposure scenario, but there are no clinically approved postexposure medical countermeasures. Here, we introduce a platform that utilizes a combination of a toxin sequestering agent and a pharmacological antagonist to ablate botulinum neurotoxicity in a well-defined mouse lethality assay. The platform was constructed to allow for ready exchange of sequestering agent and/or pharmacological antagonist for therapeutic optimization. As such, we attempted to improve upon the pharmacological antagonist, a potassium channel blocker, 3,4-diaminopyridine, through a prodrug approach; thus, a complete kinetic decomposition pathway is described. These experiments provide the first proof-of-principle that a synergistic combination strategy can be used to reduce toxin burden in the peripheral using a sequestering antibody, while restoring muscle action via a pharmacological small molecule antagonist.
Asunto(s)
4-Aminopiridina/análogos & derivados , Toxinas Botulínicas/antagonistas & inhibidores , Toxinas Botulínicas/toxicidad , Síndromes de Neurotoxicidad/tratamiento farmacológico , Bloqueadores de los Canales de Potasio/farmacología , Secuestrantes/farmacología , 4-Aminopiridina/química , 4-Aminopiridina/farmacocinética , 4-Aminopiridina/farmacología , Amifampridina , Animales , Antitoxina Botulínica/farmacología , Quimioterapia Combinada , Femenino , Cinética , Ratones , Síndromes de Neurotoxicidad/sangre , Bloqueadores de los Canales de Potasio/química , Bloqueadores de los Canales de Potasio/farmacocinética , Análisis de SupervivenciaRESUMEN
The botulinum neurotoxins, characterized by their neuromuscular paralytic effects, are the most toxic proteins known to man. Due to their extreme potency, ease of production, and duration of activity, the BoNT proteins have been classified by the Centers for Disease Control as high threat agents for bioterrorism. In an attempt to discover effective BoNT therapeutics, we have pursued a strategy in which we leverage the blockade of K(+) channels that ultimately results in the reversal of neuromuscular paralysis. Towards this end, we utilized peptides derived from scorpion venom that are highly potent K(+) channel blockers. Herein, we report the synthesis of charybdotoxin, a 37 amino acid peptide, and detail its activity, along with iberiotoxin and margatoxin, in a mouse phrenic nerve hemidiaphragm assay in the absence and the presence of BoNT/A.
Asunto(s)
Toxinas Botulínicas , Caribdotoxina/química , Parálisis/inducido químicamente , Parálisis/tratamiento farmacológico , Nervio Frénico/efectos de los fármacos , Bloqueadores de los Canales de Potasio/química , Venenos de Escorpión , Secuencia de Aminoácidos , Animales , Caribdotoxina/farmacología , Caribdotoxina/uso terapéutico , Ratones , Datos de Secuencia Molecular , Contracción Muscular/efectos de los fármacos , Péptidos/química , Péptidos/farmacología , Bloqueadores de los Canales de Potasio/farmacología , Bloqueadores de los Canales de Potasio/uso terapéutico , Resinas Sintéticas/química , Venenos de Escorpión/química , Venenos de Escorpión/farmacología , Venenos de Escorpión/uso terapéuticoRESUMEN
Small molecule probes have been used extensively to explore biologic systems and elucidate cellular signaling pathways. In this study, we use an inhibitor of bacterial communication to monitor changes in the proteome of Salmonella enterica serovar Typhimurium with the aim of discovering unrecognized processes regulated by AI-2-based quorum-sensing (QS), a mechanism of bacterial intercellular communication that allows for the coordination of gene expression in a cell density-dependent manner. In S. typhimurium, this system regulates the uptake and catabolism of intercellular signals and has been implicated in pathogenesis, including the invasion of host epithelial cells. We demonstrate that our QS antagonist is capable of selectively inhibiting the expression of known QS-regulated proteins in S. typhimurium, thus attesting that QS inhibitors may be used to confirm proposed and elucidate previously unidentified QS pathways without relying on genetic manipulation.
Asunto(s)
Técnicas de Sonda Molecular , Percepción de Quorum , Salmonella typhimurium/citología , Salmonella typhimurium/metabolismo , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Homoserina/análogos & derivados , Homoserina/metabolismo , Lactonas/metabolismo , Pentanonas/farmacología , Proteómica , Percepción de Quorum/efectos de los fármacos , ARN Mensajero/genética , ARN Mensajero/metabolismo , Salmonella typhimurium/efectos de los fármacos , Salmonella typhimurium/genéticaRESUMEN
The opportunistic bacterial pathogen Pseudomonas aeruginosa causes chronic lung infections in cystic fibrosis (CF) patients. Importantly, virulence factor expression and biofilm formation in P. aeruginosa is coordinated by quorum sensing (QS) and one of the key QS signaling molecules is 3-oxo-C12-HSL. Remarkably, a tetramic acid, (C12-TA), with antibacterial properties is formed spontaneously from 3-oxo-C12-HSL under physiological conditions. Seeking to better understand this relationship, we sought to investigate whether 3-oxo-C12-HSL and C12-TA may be contributing factors to the overall pathogenicity of P. aeruginosa in CF individuals and if their detection and quantitation in sputum samples might be used as an indicator to assess disease states and monitor therapy success in CF patients. To this end, 3-oxo-C12-HSL and C12-TA concentrations were initially analyzed in P. aeruginosa flow cell biofilms using liquid chromatography coupled with mass spectrometry (LC-MS). A liquid chromatography tandem mass spectrometry (LC-MS/MS)-based method was then developed and validated for their detection and quantification in the sputa of CF patients. To the best of our knowledge, this is the first report to show the presence of both the quorum sensing molecule (3-oxo-C12-HSL) and its rearranged product (C12-TA) in human clinical samples such as sputum. A total of 47 sputum samples from 20 CF and 2 non-CF individuals were analyzed. 3-Oxo-C12-HSL was detected and quantified in 45 samples with concentrations ranging from 20 to >1000 nM; C12-TA was found in 14 samples (13-900 nM). On the basis of our findings, quorum sensing autoinducers merit further investigation as biomarkers for infectious disease states.
Asunto(s)
Pseudomonas aeruginosa/aislamiento & purificación , Percepción de Quorum , Espectrometría de Masa por Ionización de Electrospray/métodos , Esputo/química , Adolescente , Adulto , Biomarcadores/análisis , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infecciones por Pseudomonas/diagnóstico , Adulto JovenRESUMEN
Bacteria have developed cell-to-cell communication mechanisms, termed quorum sensing (QS), that regulate bacterial gene expression in a cell population-dependent manner. Autoinducer-2 (AI-2), a class of QS signaling molecules derived from (4S)-4,5-dihydroxy-2,3-pentanedione (DPD), has been identified in both Gram-negative and Gram-positive bacteria. Despite considerable interest in the AI-2 QS system, the biomolecular communication used by distinct bacterial species still remains shrouded. Herein, we report the synthesis and evaluation of a new class of DPD analogues, C4-alkoxy-5-hydroxy-2,3-pentanediones, termed C4-alkoxy-HPDs. Remarkably, two of the analogues were more potent QS agonists than the natural ligand, DPD, in Vibrio harveyi. The findings presented extend insights into ligand-receptor recognition/signaling in the AI-2 mediated QS system.
Asunto(s)
Antibacterianos/química , Antibacterianos/farmacología , Pentanos/química , Pentanos/farmacología , Percepción de Quorum/efectos de los fármacos , Vibrio/efectos de los fármacos , Antibacterianos/síntesis química , Descubrimiento de Drogas , Humanos , Pentanos/síntesis química , Vibrio/metabolismo , Vibriosis/tratamiento farmacológicoRESUMEN
Bacteria use small diffusible molecules to exchange information in a process called quorum sensing (QS). An important class of quorum sensing molecules used by Gram-negative bacteria is the family of N-acylhomoserine lactones (HSL). It was recently discovered that a degradation product of the QS molecule 3-oxo-C(12)-homoserine lactone, the tetramic acid 3-(1-hydroxydecylidene)-5-(2-hydroxyethyl)pyrrolidine-2,4-dione, is a potent antibacterial agent, thus implying roles for QS outside of simply communication. Because these tetramic acids also appear to bind iron with appreciable affinity it was suggested that metal binding might contribute to their biological activity. Here, using a variety of spectroscopic tools, we describe the coordination chemistry of both the methylidene and decylidene tetramic acid derivatives with Fe(III) and Ga(III) and discuss the potential biological significance of such metal binding.
Asunto(s)
4-Butirolactona/análogos & derivados , Antibacterianos/química , Complejos de Coordinación/química , Galio/química , Hierro/química , Succinimidas/química , 4-Butirolactona/química , Antibacterianos/farmacología , Complejos de Coordinación/farmacología , Electroquímica , Concentración de Iones de Hidrógeno , Pruebas de Sensibilidad Microbiana , Pseudomonas aeruginosa/efectos de los fármacos , Pseudomonas aeruginosa/crecimiento & desarrollo , Percepción de Quorum , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/crecimiento & desarrollo , Succinimidas/farmacologíaRESUMEN
Multivalency is a common principle in the recognition of cellular receptors, and multivalent agonists and antagonists have played a major role in understanding mammalian cell receptor biology. The study of bacterial cell receptors using similar approaches, however, has lagged behind. Herein we describe our efforts toward the development of a dendrimer-based multivalent probe for studying AI-2 quorum-sensing receptors. From these studies, we have discovered a chemical probe specific for Lsr-type AI-2 quorum-sensing receptors with the potential for enabling the identification of new bacterial species that utilize AI-2 as a quorum-sensing signaling molecule.
Asunto(s)
Bacterias/citología , Dendrímeros/química , Colorantes Fluorescentes/química , Pentanos/química , Percepción de Quorum , Bacillus cereus/citología , Microscopía Fluorescente/métodos , Modelos Moleculares , Rodaminas/química , Salmonella typhimurium/citología , Vibrio/citologíaRESUMEN
Bacteria have developed a cell-to-cell communication system, termed quorum sensing (QS), which allows for the population-dependent coordination of their behavior via the exchange of chemical signals. Autoinducer-2 (AI-2), a class of QS signals derived from 4,5-dihydroxy-2,3-pentandione (DPD), has been revealed as a universal signaling molecule in a variety of bacterial species. In spite of considerable interest, the study of putative AI-2 based QS systems remains a challenging topic in part due to the rapid interconversion between the linear and cyclic forms of DPD. Herein, we report the design and development of efficient syntheses of carbocyclic analogues of DPD, which are locked in the cyclic form. The synthetic analogues were evaluated for the modulation of AI-2-based QS in Vibrio harveyi and Salmonella typhimurium. No agonists were uncovered in either V. harveyi or S. typhimurium assay, whereas weak to moderate antagonists were found against V. harveyi. On the basis of NMR analyses and DFT calculations, the heterocyclic oxygen atom within DPD appears necessary to promote hydration at the C3 position of cyclic DPD to afford the active tetrahydroxy species. These results also shed light on the interaction between the heterocyclic oxygen atom and receptor proteins as well as the importance of the linear form and dynamic equilibrium of DPD as crucial requirements for activation of AI-2 based QS circuits.
Asunto(s)
Homoserina/análogos & derivados , Lactonas/química , Percepción de Quorum , Homoserina/síntesis química , Homoserina/química , Lactonas/síntesis química , Espectroscopía de Resonancia Magnética , Estructura Molecular , Pentanonas/síntesis química , Pentanonas/química , Teoría Cuántica , Salmonella typhimurium/química , Salmonella typhimurium/metabolismo , Vibrio/química , Vibrio/metabolismoRESUMEN
The triphenyl amide/ester 12 was originally reported to be a potent mimic of the natural 3-oxo-dodecanoyl homoserine lactone quorum sensing molecule in Pseudomonas aeruginosa. However, explicit synthesis/chemical characterization was lacking, and a later report providing protein crystallographic data inferred 12 to be incorrect, with 9 now being the surmised structure. Because of these inconsistencies and our interest in quorum sensing molecules utilized by gram-negative bacteria, we found it necessary to synthesize 9 and 12 to test for agonistic activity in a P. aeruginosa reporter assay. Despite distinct regiochemical differences, both 9 and 12 were found to have comparable EC(50) values. To reconcile these unanticipated findings, modeling studies were conducted, and both compounds were revealed to have comparable properties for binding to the LasR receptor.
Asunto(s)
4-Butirolactona/análogos & derivados , Modelos Moleculares , Pseudomonas aeruginosa/fisiología , Percepción de Quorum , 4-Butirolactona/síntesis químicaRESUMEN
Within environmental communities, there is a constant struggle for survival, as nutrients are often limited. In response, bacteria have developed elaborate methods to deal with competitors. One such mechanism is the coordination of behaviors and function via the exchange of small chemical signals in a process known as quorum sensing. This process is especially prominent in the pathogenicity of Pseudomonas aeruginosa, an opportunistic human pathogen that forms sessile communities known as biofilms. These biofilms play an important role in the lifestyle of P. aeruginosa, either in their natural environment or during establishment and maintenance of infection in human hosts; thus, they often have grievous effects on human health. As such, a method for the detection of these QS signals may provide insights into the pathogenicity and survival of P. aeruginosa. In this chapter, we present a method for the extraction and quantitation of the P. aeruginosa QS signal N-3-oxo-dodecanoyl-homoserine lactone, and its rearranged tetramic acid product, C12-TA, which itself has implications as a survival tactic used by P. aeruginosa.
Asunto(s)
4-Butirolactona/análogos & derivados , Dimerización , Homoserina/análogos & derivados , Pseudomonas aeruginosa/química , 4-Butirolactona/análisis , 4-Butirolactona/química , 4-Butirolactona/aislamiento & purificación , Biopelículas , Fraccionamiento Químico , Cromatografía Liquida , Homoserina/análisis , Homoserina/química , Homoserina/aislamiento & purificación , Espectrometría de Masas , Microscopía Confocal , Pseudomonas aeruginosa/fisiología , Reproducibilidad de los ResultadosRESUMEN
Alkynyl- and azido-tagged 3-oxo-C(12)-acylhomoserine lactone probes have been synthesized to examine their potential utility as probes for discovering the mammalian protein target of the Pseudomonas aeruginosa autoinducer, 3-oxo-C(12)-acylhomoserine lactone. Although such substitutions are commonly believed to be quite conservative, from these studies, we have uncovered a drastic difference in activity between the alkynyl- and azido-modified compounds, and provide an example where such structural modification has proved to be much less than conservative.
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Células/efectos de los fármacos , Homoserina/síntesis química , Homoserina/farmacología , Lactonas/síntesis química , Pseudomonas/metabolismo , Percepción de Quorum , Alanina/análogos & derivados , Alanina/farmacología , Animales , Química Clic , Homoserina/química , Humanos , Lactonas/química , Lactonas/farmacología , Estructura Molecular , Pseudomonas/químicaAsunto(s)
Antibacterianos/química , Percepción de Quorum/efectos de los fármacos , Acil-Butirolactonas/química , Acil-Butirolactonas/metabolismo , Acil-Butirolactonas/farmacología , Animales , Antibacterianos/farmacología , Descubrimiento de Drogas , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Homoserina/análogos & derivados , Homoserina/química , Homoserina/farmacología , Homoserina/fisiología , Humanos , Lactonas/química , Lactonas/farmacología , Estructura Molecular , Pentanos/química , Pentanos/metabolismo , Pentanos/farmacología , Péptidos Cíclicos/química , Péptidos Cíclicos/farmacología , Péptidos Cíclicos/fisiología , Relación Estructura-ActividadRESUMEN
Despite significant progress and notable successes in tumor therapy, malignant disease remains an extremely difficult problem in today's health care setting. There is, however, an increasing application of new therapies targeting proteins specifically upregulated on tumor cells. These innovative therapeutic approaches are aimed at molecules that contribute to malignant development and progression but spare normal tissues. The CUB domain containing protein 1 (CDCP1) is such a tumor-associated protein and, thus, a potential candidate for targeted cancer immunotherapy. Herein, we describe the generation of function-blocking human antibodies against CDCP1 that were obtained from human scFv phage display libraries using subtractive panning protocols on CDCP1 expressing cancer cells and immunopurified CDCP1 protein. One of the isolated anti-CDCP1 antibodies, namely, C20Fc, efficiently blocked experimental metastasis of human carcinoma cells, including HeLa cells stably transfected with CDCP1 and prostate carcinoma cells PC-hi/diss naturally expressing CDCP1, in both chick embryo and mouse model systems. The C20Fc antibody also reduced colony formation of CDCP1 expressing cells in a soft agar assay for anchorage-independent cell growth. Specific targeting of CDCP1 by C20Fc mediated the delivery of a toxin-conjugated antibody complex, thus, providing evidence for antibody internalization and specific killing of CDCP1-positive tumor cells. Our findings indicate a functional role for CDCP1 in human cancer and underscore the therapeutic potential of function-blocking anti-CDCP1 antibodies targeting both primary and metastatic carcinoma cells.
Asunto(s)
Antígenos CD/inmunología , Moléculas de Adhesión Celular/antagonistas & inhibidores , Moléculas de Adhesión Celular/inmunología , Metástasis de la Neoplasia/prevención & control , Proteínas de Neoplasias/antagonistas & inhibidores , Proteínas de Neoplasias/inmunología , Secuencia de Aminoácidos , Animales , Anticuerpos Bloqueadores/administración & dosificación , Anticuerpos Bloqueadores/genética , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/genética , Citotoxicidad Celular Dependiente de Anticuerpos , Antígenos CD/genética , Antígenos de Neoplasias , Moléculas de Adhesión Celular/genética , Línea Celular Tumoral , Embrión de Pollo , Femenino , Células HeLa , Humanos , Masculino , Ratones , Ratones Endogámicos NOD , Ratones SCID , Datos de Secuencia Molecular , Metástasis de la Neoplasia/inmunología , Metástasis de la Neoplasia/terapia , Proteínas de Neoplasias/genética , Biblioteca de Péptidos , Neoplasias de la Próstata/inmunología , Neoplasias de la Próstata/secundario , Neoplasias de la Próstata/terapia , Proteínas Recombinantes de Fusión/administración & dosificación , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/inmunología , Homología de Secuencia de Aminoácido , Transfección , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Quorum sensing (QS) systems have been discovered in a wide variety of bacteria, and mediate both intra- and interspecies communication. The AI-2-based QS system represents the most studied of these proposed interspecies systems and has been shown to regulate diverse functions such as bioluminescence, expression of virulence factors, and biofilm formation. As such, the development of modulatory compounds, both agonists and antagonists, is of great interest for the study of unknown AI-2-based QS systems and the potential treatment of bacterial infections. The fimbrolide class of natural products has exhibited excellent inhibitory activity against AI-2-based QS and as such may be considered the "gold standard" of AI-2 inhibitors. Thus, we sought to include a fimbrolide as a control compound for our recently developed alkyl-DPD panel of AI-2 modulators. Herein, we present a revised synthesis of a commonly studied fimbrolide as well as a direct comparison between the fimbrolide and alkyl-DPD analogues. We demonstrate that our alkyl-DPD analogues are more potent inhibitors of QS in both Vibrio harveyi and Salmonella typhimurium, the two organisms with defined AI-2 QS systems, and in doing so call into question the widely accepted use of fimbrolide-derived compounds as the "gold standard" of AI-2 inhibition.
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Productos Biológicos/química , Furanos/química , Percepción de Quorum/efectos de los fármacosRESUMEN
In nature, bacteria rarely exist as single, isolated entities, but rather as communities comprised of many other species including higher host organisms. To survive in these competitive environments, microorganisms have developed elaborate tactics such as the formation of biofilms and the production of antimicrobial toxins. Recently, it was discovered that the gram-negative bacterium Pseudomonas aeruginosa , an opportunistic human pathogen, produces an antibiotic, 3-(1-hydroxydecylidene)-5-(2-hydroxyethyl)pyrrolidine-2,4-dione (C(12)-TA), derived from one of its quorum sensing molecules. Here, we present a comprehensive study of the expanded spectrum of C(12)-TA antibacterial activity against microbial competitors encountered by P. aeruginosa in nature as well as significant human pathogens. The mechanism of action of C(12)-TA was also elucidated, and C(12)-TA was found to dissipate both the membrane potential and the pH gradient of Gram-positive bacteria, correlating well with cell death. Notably, in stark contrast to its parent molecule 3-oxo-dodecanoyl homoserine lactone (3-oxo-C(12)-HSL), neither activation of cellular stress pathways nor cytotoxicity was observed in human cells treated with C(12)-TA. Our results suggest that the QS machinery of P. aeruginosa has evolved for a dual-function, both to signal others of the same species and also to defend against host immunity and competing bacteria. Because of the broad-spectrum antibacterial activity, established mode of action, lack of rapid resistance development, and tolerance by human cells, the C(12)-TA scaffold may also serve as a new lead compound for the development of antimicrobial therapeutics.
Asunto(s)
Antibacterianos/farmacología , Pseudomonas aeruginosa/química , Pirrolidinonas/farmacología , 4-Butirolactona/análogos & derivados , 4-Butirolactona/farmacología , Antibacterianos/biosíntesis , Antibacterianos/química , Bacterias Grampositivas/efectos de los fármacos , Humanos , Potenciales de la Membrana/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Pseudomonas aeruginosa/metabolismo , Pirrolidinas/química , Pirrolidinas/farmacología , Percepción de QuorumRESUMEN
Quorum sensing (QS) has traditionally referred to a mechanism of communication within a species of bacteria. However, emerging research implicates QS in interspecies communication and competition, and such systems have been proposed in a wide variety of bacteria. The AI-2-based QS system represents the most studied of these proposed interspecies systems, and has been proposed to regulate diverse functions such as bioluminescence, expression of virulence factors, and biofilm formation. As such, the development of modulatory compounds, both agonists and antagonists, is of great interest for the treatment of bacterial infections and the study of unknown AI-2-based QS systems. Toward this end, we have designed and synthesized a panel of 4,5-dihydroxy-2,3-pentanedione/AI-2 analogues and evaluated their effects on the AI-2 QS of various bacteria. The panel of compounds exhibited differential effects in the bacterial cell lines examined, providing a platform for the development of broad-spectrum modulators of AI-2-based QS.
Asunto(s)
Homoserina/análogos & derivados , Lactonas/metabolismo , Pentanonas/síntesis química , Pentanonas/farmacología , Percepción de Quorum/efectos de los fármacos , Inducción Enzimática , Homoserina/química , Homoserina/metabolismo , Lactonas/química , Mediciones Luminiscentes , Pentanonas/química , Salmonella typhimurium/enzimología , Salmonella typhimurium/metabolismo , Salmonella typhimurium/fisiología , Vibrio/metabolismo , Vibrio/fisiología , beta-Galactosidasa/biosíntesisRESUMEN
Quorum sensing (QS) has traditionally referred to a mechanism of communication within a species of bacteria. However, emerging research implicates QS in interspecies communication and competition, and such systems have been proposed in a wide variety of bacteria. This activity of bacterial QS also extends to relationships between bacteria and eukaryotes and host-pathogen interactions in both clinical and agricultural settings are of particular interest. These relationships are particularly pertinent in light of the rising prevalence of antibiotic resistant bacteria. In this tutorial review we describe bacterial QS and its capacity in interspecies and interkingdom interactions, as well as the corresponding eukaryotic responses.
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Antibacterianos/farmacología , Bacterias/metabolismo , Comunicación Celular/fisiología , Células Eucariotas/fisiología , Percepción de Quorum/fisiología , Antibacterianos/química , Bacterias/genética , Bacterias/crecimiento & desarrollo , Proteínas Bacterianas/genética , Proteínas Bacterianas/fisiología , Comunicación Celular/genética , Células Eucariotas/inmunología , Regulación Bacteriana de la Expresión Génica , Percepción de Quorum/genética , Transducción de SeñalRESUMEN
An autoinducer arising from reaction of cyclized S-DPD and carbonate is shown to induce light in V. harveyi and thus may play a previously unknown role in quorum sensing.