Bacteria use small chemical molecules called autoinducers to communicate with one another by a process called quorum sensing. This process enables a population of bacteria to regulate behaviours which are only productive when many bacteria act in concert as a group, similarly to what happens with multi-cellular organisms. Behaviours regulated by quorum sensing are often crucial for successful bacterial-host relationships whether symbiotic and pathogenic.
In this laboratory biochemical and genetic approaches are used to study the molecular mechanisms underlying quorum sensing, with an emphasis on systems promoting bacterial inter-species communication. This research includes an integrated study involving elucidation of the chemical molecules that are used as signals, the network components involved in detecting the signals and processing information inside individual cells, and finally characterization of the behaviour of the bacterial community in multi-species bacterial consortia. Our ultimate goal is to understand how bacteria use inter-species cell-cell communication to coordinate population-wide behaviours in consortia and in microbial-host interactions.
Karina B. Xavier – Biography
Our laboratory is seeking highly motivated post doctoral fellows and students. Click here for more details.
Interspecies Signaling in Bacterial Communities
We are studying interspecies cell-to-cell communication in bacteria and its role in beneficial and hostile interactions in the bacterial communities of the mammalian gut. Our aims include establishing strategies to tailor gut microbiota composition and to profit from its protective function against infectious and inflammatory diseases.
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Howard Hughes Medical Institute
HHMI International Early Career Award LINK
Inter-species cell-cell signalling in bacteria
This project focuses on the molecular mechanisms that bacteria use for inter-cellular communication. This process, called quorum sensing, involves the production, release, and response to signal molecules termed autoinducers. Quorum sensing enables a bacterial population to regulate activities as a multi-cellular group. Most autoinducers are species-specific, however one autoinducer called autoinducer-2 (AI-2), is produced and detected by a wide variety of bacteria allowing inter-species communication. This project relies on a multi-disciplinary approach to study AI-2 systems promoting bacterial inter-species communication. By studying quorum sensing in Escherichia coli, we have characterized one of the first AI-2 systems. We will pursue the characterization of the E. coli AI-2 system, and will also investigate novel AI-2 signalling systems in other bacteria to understand the network architecture controlling AI-2 signalling at the species level. We have developed the first laboratory system to study inter-species AI-2 signalling in consortia, so once we identify novel AI-2 circuits, we will use this set up to study inter-species cell-cell communication in complex bacterial communities.
Marie Curie International Reintegration Grant (031108),
European Commission, and Luso-American Foundation (FLAD) (Portugal)
U.S. NATIONAL SCIENCE FOUNDATION (NSF) Research Network Grants (Proj. 600-10/2006).
Bonnie L. Bassler
Identification and characterization of quorum sensing systems involved in bacterial inter-species communication
Many quorum sensing systems have been extensively studied and are well characterized, in some cases new therapies are already being developed to interfere with quorum sensing to inhibit virulence. In most cases quorum sensing systems are regulated by species specific autoinducers and are used for bacterial intra-species communication. In contrast, one autoinducer, termed autoinducer-2 (AI-2), is produced and detected by a wide variety of bacteria and is considered a “universal” bacterial signal that fosters inter-species communication. Since the discovery of AI-2, many laboratories have shown that different bacteria use AI-2 to control an assortment of “niche-specific” behaviours. However, the mechanisms of AI-2 detection and the cognate signal transduction pathways have only been established in two Vibrio species and the enteric bacteria Escherichia coli and Salmonella enteric serovar Typhimurium
The research undertaken in this project involves a biochemical, genetic, and chemical characterization of novel AI-2 signalling systems. Our preliminary results show that the plant symbiont Sinorhizobium meliloti
has an AI-2 internalization system similar to the E. coli
AI-2 system and we will characterize this system in detail to evaluate its function during the symbiosis S. meliloti
establishes with its host the alfalfa plant. Furthermore, to assess the diversity of these systems we will identify and characterize AI-2 detection systems from additional bacterial species, and determine the structure of novel AI-2 signal-receptor complexes to identify the active AI-2 molecules. Mutants impaired in these AI-2 signalling pathways will be constructed, characterized, and used to study bacterial-bacterial, and bacterial-host interactions.
Projectos de I&D - Fundação para a Ciência e Tecnologia
Identification and characterization of quorum sensing systems involved in bacterial inter-species communication (PTDC/BIA-BCM/73676/2006)
Stephen T. Miller
Quorum Sensing in Escherichia coli
This project relies on a multidisciplinary approach to investigate the molecular mechanisms underlying AI-2 quorum sensing in the enteric bacterium Escherichia coli, with an emphasis on its role in bacterial inter-species communication. We have showed that, in E. coli, AI-2-regulates a system that internalizes and degrades the AI-2 signal. Specifically, at high population densities, E. coli uses this system to remove AI-2 produced by itself and also AI-2 produced by other species present in the same co-culture. AI-2 internalization by E. coli has the consequence of interfering with other species’ ability to use AI-2 to regulate their group behaviours by quorum sensing. We predict that this mechanism of interference with AI-2 signalling has important consequences in natural niches colonized by E. coli such as the human gut where many different species of bacterial species co-exist and depend on quorum sensing for efficient colonization.
The E. coli AI-2 internalization process represents the first example of interference with AI-2-mediated quorum sensing. Understanding the natural strategies organisms use to interfere with other species’ ability to communicate, such as in E. coli, can be used as models in the design of clinical and biotechnological strategies intended to manipulate bacterial behaviours. Such studies can lead to the development of new therapies to control functions regulated by quorum sensing, such as virulence, and also to develop biotechnological applications to control industrial scale production of beneficial bacterial products, like antibiotics or recombinant proteins.
Programa Damião de Góis – Fundação para a Ciência e Tecnologia
Quorum Sensing in Escherichia coli (PPCDT/DG/BIA/82010/2006)
10 SELECTED PUBLICATIONS
Pereira, C.S., Thompson, J.A., Xavier, K.B. (2013)
AI-2-mediated signalling in bacteria
FEMS Microbiol Rev
37 : 156-181
Pereira, C.S., Santos, A.J.M., Bejerano-Sagie, M., Correia, P.B., Marques, J.C., Xavier, K.B. (2012)
Phosphoenolpyruvate Phosphotransferase System regulates detection and processing of the quorum sensing signal Autoinducer-2
84 : 93-104
Nadal Jimenez, P., Koch, G., Thompson, J.A., Xavier, K.B., Cool, R.H., Quax, W. J. (2012)
The Multiple Signaling Systems Regulating Virulence in Pseudomonas aeruginosa
Microbiol Mol Biol Rev
76(4) : 46-65
Marques, J.C., Lamosa, P., Russell, C., Ventura, R., Maycock, C., Semmelhack, M.F., Miller, S.T., Xavier, K.B. (2011)
Processing the interspecies quorum-sensing signal autoinducer-2 (AI-2): characterization of phospho-(S)-4,5-dihydroxy-2,3-pentanedione isomerization by LsrG protein
J Biol Chem
286 : 18331-43
Pereira, C.S., de Regt, A.K., Brito, P.H, Miller, S.T., Xavier, K.B. (2009)
Identification of functional LsrB-like autoinducer-2 receptors
191 : 6975-87
Pereira, C.S., McAuley, J.R., Taga, M. E., Xavier, K. B., Miller, S.T. (2008)
Sinorhizobium meliloti, a bacterium lacking the autoinducer-2 synthase, responds to AI-2 supplied by other bacteria
70 : 1223-35
Bejerano-Sagie, M., Xavier, K.B. (2007)
The Role of Small RNAs in Quorum-Sensing
Curr Opin Microbiol
10 : 189-98
Xavier, K.B., Bassler, B.L. (2005)
Interference with AI-2-mediated bacterial cell-cell communication
437 : 750-753
Xavier, K.B., Bassler, B.L. (2005)
Regulation of uptake and processing of the quorum-sensing autoinducer AI-2 in Escherichia coli
187 : 238-48
Miller, S.T., Xavier, K.B., Campagna, S.R., Taga, M.E., Semmelhack, M.F., Bassler, B.L., Hughson, F.M. (2004)
Salmonella typhimurium recognizes a chemically distinct form of the bacterial quorum-sensing signal AI-2
15 : 677-87