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Honors & Awards

Bonnie L. Bassler

Squibb Professor in Molecular Biology
Chair, department of molecular biology
 

 

Bonnie Bassler

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phone (609) 258-2857
locationLewis Thomas Lab, 329
phone Lab (609) 258-2864
 
 
Faculty Assistant
Jennifer Munko
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phone (609) 258-5659

 

Research Focus

Cell-to-Cell Communication in Bacteria

The research in my laboratory focuses on the molecular mechanisms that bacteria use for intercellular communication. Our goal is to understand how bacteria detect multiple environmental cues, and how the integration and processing of this information results in the precise regulation of gene expression.

The bacterial communication phenomenon that we study is called quorum sensing, which is a process that allows bacteria to communicate using secreted chemical signaling molecules called autoinducers. This process enables a population of bacteria to collectively regulate gene expression and, therefore, behavior. In quorum sensing, bacteria assess their population density by detecting the concentration of a particular autoinducer, which is correlated with cell density. This "census-taking" enables the group to express specific genes only at particular population densities. Quorum sensing is widespread; it occurs in numerous Gram-negative and Gram-positive bacteria. In general, processes controlled by quorum sensing are ones that are unproductive when undertaken by an individual bacterium but become effective when undertaken by the group. For example, quorum sensing controls bioluminescence, secretion of virulence factors, sporulation, and conjugation. Thus, quorum sensing is a mechanism that allows bacteria to function as multi-cellular organisms.

We have shown that the model luminous bacterium Vibrio harveyi and the related pathogen Vibrio cholerae each produce two different autoinducers, called AI-1 and AI-2, each of which is detected by its own sensor protein. Both sensors transduce information to a shared integrator protein to control the output, light emission in V. harveyi and virulence in V. cholerae. We have cloned the genes for signal production, detection and response in both species and have shown that the mechanism of signal relay is a phosphorylation/dephosphorylation cascade. Our recent studies combining genetics and bioinformatics (in collaboration with the Wingreen lab) show that the small RNA chaperone protein Hfq, together with multiple small regulatory RNAs (sRNAs), act at the center of these quorum sensing cascades. They function as an ultrasensitive regulatory switch that controls the critical transition into and out of quorum sensing mode.

V. harveyi and V. cholerae use the AI-1 quorum sensing circuit for intra-species communication and the AI-2 quorum sensing circuit for inter-species communication. To investigate the mechanism of AI-2 signaling, we constructed mutants and cloned the gene responsible for AI-2 production from several bacteria. The gene we identified in each case is highly homologous, and we named it luxS. We found that luxS homologues and AI-2 production are widespread in the bacterial world, suggesting that communication via an AI-2 signal response system could be a common mechanism that bacteria employ for inter-species interaction in natural environments. We determined the biosynthetic pathway for AI-2 production as well as the AI-2 identity by solving the crystal structures of the V. harveyi and S. typhimurium sensor proteins in complex with their cognate AI-2 signals. The structural work was performed in collaboration with the Hughson lab. The V. harveyi AI-2 is a furanosylborate diester. Finding boron in the active molecule was surprising because boron, while widely available in nature has almost no known role in biology. The S. typhimurium crystal showed that its receptor binds a chemically distinct AI-2 that lacks borate. Importantly, the active signal molecules spontaneously inter-convert upon release from their respective receptors, revealing a surprising level of sophistication in the chemical lexicon used by bacteria for inter-species cell-cell communication.

Finally, we are focused on developing molecules that are structurally related to AI-2. Such molecules have potential use as anti-microbial drugs aimed at bacteria that use AI-2 quorum sensing to control virulence. Similarly, the biosynthetic enzymes involoved in AI-2 production and the AI-2 detection apparatuses are viewed as potential targets for novel anti-microbial drug design.


Selected Publications

Perez LJ, Karagounis TK, Hurley A, Bassler BL, Semmelhack MF. (2014) Highly otent, chemically stable quorum sensing agonists for Vibrio cholerae. Chem Sci. 5: 151-155. Pubmed

Ke X, Miller LC, Ng WL, Bassler BL. (2013) CqsA-CqsS quorum-sensing signal-receptor specificity in Photobacterium angustum. Mol Microbiol. [Epub ahead of print]

Drescher K, Nadell CD, Stone HA, Wingreen NS, Bassler BL. (2013) Solutions to the public goods dilemma in bacterial biofilms. Curr Biol. 24: 50-5. Pubmed

O'Loughlin CT, Miller LC, Siryaporn A, Drescher K, Semmelhack MF, Bassler BL. (2013) A quorum-sensing inhibitor blocks Pseudomonas aeruginosa virulence and biofilm formation. Proc Natl Acad Sci. 110: 17981-6. Pubmed

van Kessel JC, Ulrich LE, Zhulin IB, Bassler BL. (2013) Analysis of activator and repressor functions reveals the requirements for transcriptional control by LuxR, the master regulator of quorum sensing in Vibrio harveyi. MBio. 4. pii: e00378-13. Pubmed

Shao Y, Feng L, Rutherford ST, Papenfort K, Bassler BL. (2013) Functional determinants of the quorum-sensing non-coding RNAs and their roles in target regulation. EMBO J. 32: 2158-71. Pubmed

van Kessel JC, Rutherford ST, Shao Y, Utria AF, Bassler BL.(2013) Individual and combined roles of the master regulators AphA and LuxR in control of the Vibrio harveyi quorum-sensing regulon. J Bacteriol. 195: 436-43. Pubmed

Drescher K, Shen Y, Bassler BL, Stone HA. (2013) Biofilm streamers cause catastrophic disruption of flow with consequences for environmental and medical systems. Proc Natl Acad Sci. 110: 4345-50. Pubmed

Nadell CD, Bucci V, Drescher K, Levin SA, Bassler BL, Xavier JB. (2013) Cutting through the complexity of cell collectives. Proc Biol Sci. 280: 20122770. Pubmed

van Kessel JC, Rutherford ST, Shao Y, Utria AF, Bassler BL. (2012) The master regulators AphA and LuxR control the Vibrio harveyi quorum-sensing regulon: analysis of their individual and combined effects. J Bacteriol. 195: 436-43. Pubmed

Rutherford ST, Bassler BL. (2012) Bacterial quorum sensing: its role in virulence and possibilities for its control. Cold Spring Harb Perspect Med. 2 pii: a012427. Pubmed

Perez LJ, Ng WL, Marano P, Brook K, Bassler BL, Semmelhack MF. (2012) Role of the CAI-1 Fatty Acid Tail in the Vibrio cholerae Quorum Sensing Response. J Med Chem. 55: 9669-9681. Pubmed

Ng WL, Perez L, Cong J, Semmelhack MF, Bassler BL. (2012) Broad spectrum pro-quorum-sensing molecules as inhibitors of virulence in vibrios. PLoS Pathog. 8: e1002767. Pubmed

Shao Y, Bassler BL. (2012) Quorum-sensing non-coding small RNAs use unique pairing regions to differentially control mRNA targets. Mol Microbiol. 83: 599-611. PubMed

Wei Y, Ng WL, Cong J, Bassler BL. (2012) Ligand and antagonist driven regulation of the Vibrio cholerae quorum-sensing receptor CqsS. Mol Microbiol. 83: 1095-1108. PubMed

Chen G, Swem LR, Swem DL, Stauff DL, O'Loughlin CT, Jeffrey PD, Bassler BL, Hughson FM. (2011) A strategy for antagonizing quorum sensing. Mol Cell. 42: 199-209. PubMed

Rutherford ST, van Kessel JC, Shao Y, Bassler BL. (2011) AphA and LuxR/HapR reciprocally control quorum sensing in vibrios. Genes Dev. 25: 397-408. PubMed

Wei Y, Perez LJ, Ng WL, Semmelhack MF, Bassler BL. (2011) Mechanism of Vibrio cholerae autoinducer-1 Biosynthesis. ACS Chem Biol. 6: 356-365. PubMed

Ng WL, Perez LJ, Wei Y, Kraml C, Semmelhack MF, Bassler BL. (2011) Signal production and detection specificity in Vibrio CqsA/CqsS quorum-sensing systems. Mol Microbiol. 79: 1407-1417. PubMed

Bassler BL. (2010) Small cells--big future. Mol Biol Cell. 21: 3786-3787. PubMed

Waters CM, Wu JT, Ramsey ME, Harris RC, Bassler BL. (2010) Quorum sensing controls type three secretion in Vibrio harveyi through repression of ExsA. Appl Environ Microbiol. 76: 4996-5004. PubMed

Teng SW, Wang Y, Tu KC, Long T, Mehta P, Wingreen NS, Bassler BL, Ong NP. (2010) Measurement of the copy number of the master quorum-sensing regulator of a bacterial cell. Biophys J. 98: 2024-2031. PubMed

Ng WL, Wei Y, Perez LJ, Cong J, Long T, Koch M, Semmelhack MF, Wingreen NS, Bassler BL. (2010) Probing bacterial transmembrane histidine kinase receptor-ligand interactions with natural and synthetic molecules. Proc Natl Acad Sci. 107: 5575-5580. PubMed

Tu KC, Long T, Svenningsen SL, Wingreen NS, Bassler BL. (2010) Negative feedback loops involving small regulatory RNAs precisely control the Vibrio harveyi quorum-sensing response. Mol Cell. 37: 567-579. PubMed

Mehta P, Goyal S, Long T, Bassler BL, Wingreen NS. (2009) Information processing and signal integration in bacterial quorum sensing. Mol Syst Biol. 5: 325. PubMed

Kelly RC, Bolitho ME, Higgins DA, Lu W, Ng WL, Jeffrey PD, Rabinowitz JD, Semmelhack MF, Hughson FM, Bassler BL. (2009) The Vibrio cholerae quorum-sensing autoinducer CAI-1: analysis of the biosynthetic enzyme CqsA. Nat Chem Biol. 5: 891-895. PubMed

Ng WL, Bassler BL. (2009) Bacterial quorum-sensing network architectures. Annu Rev Genet. 43: 197-222. PubMed

Swem LR, Swem DL, O'Loughlin CT, Gatmaitan R, Zhao B, Ulrich SM, Bassler BL. (2009) A quorum-sensing antagonist targets both membrane-bound and cytoplasmic receptors and controls bacterial pathogenicity. Mol Cell. 35: 143-153. PubMed

Long T, Tu KC, Wang Y, Mehta P, Ong NP, Bassler BL, Wingreen NS. (2009) Quantifying the integration of quorum-sensing signals with single-cell resolution. PLoS Biol. 7: e68 PubMed

Svenningsen SL, Tu KC, Bassler BL. (2009) Gene dosage compensation calibrates four regulatory RNAs to control Vibrio cholerae quorum sensing. EMBO J. 28: 429-439. PubMed

Hammer BK, Bassler BL. (2008) Distinct sensory pathways in Vibrio cholerae El Tor and Classical biotypes modulate c-di-GMP levels to control biofilm formation. J Bacteriol. 191: 169-177. PubMed

Nadell CD, Bassler BL, Levin SA. (2008) Observing bacteria through the lens of social evolution. J Biol. 7: 27. PubMed

Tu KC, Waters CM, Svenningsen SL, Bassler BL. (2008) A small-RNA-mediated negative feedback loop controls quorum-sensing dynamics in Vibrio harveyi. Mol Microbiol. 70: 896-907. PubMed

Pompeani AJ, Irgon JJ, Berger MF, Bulyk ML, Wingreen NS, Bassler BL. (208) The Vibrio harveyi master quorum-sensing regulator, LuxR, a TetR-type protein is both an activator and a repressor: DNA recognition and binding specificity at target promoters. Mol Microbiol. 70: 76-88. PubMed

Swem LR, Swem DL, Wingreen NS, Bassler BL. (2008) Deducing receptor signaling parameters from in vivo analysis: LuxN/AI-1 quorum sensing in Vibrio harveyi. Cell 134: 461-473. PubMed

Waters CM, Lu W, Rabinowitz JD, Bassler BL. (2008) Quorum sensing controls biofilm formation in Vibrio cholerae through modulation of cyclic di-GMP levels and repression of vpsT. J Bacteriol. 190: 2527-2536. PubMed

Svenningsen SL, Waters CM, Bassler BL. (2008) A negative feedback loop involving small RNAs accelerates Vibrio cholerae's transition out of quorum-sensing mode. Genes Dev. 22: 226-238. PubMed

Rader BA, Campagna SR, Semmelhack MF, Bassler BL, Guillemin K.. (2007) The quorum sensing molecule AI-2 regulates motility and flagellar morphogenesis in Helicobacter pylori. J Bacteriol 189: 6109-6117. PubMed

Hammer BK and Bassler BL. (2007) Regulatory small RNAs circumvent the conventional quorum sensing pathway in pandemic Vibrio cholerae. Proc Natl Acad Sci USA 104: 11145-11149 PubMed

Bassler BL. (2007) Playing the game with nature. Biotechniques. 42: 123. PubMed

Xavier KB, Miller ST, Lu W, Kim JH, Rabinowitz J, Pelczer I, Semmelhack MF, Bassler BL. (2007) Phosphorylation and processing of the quorum-sensing molecule autoinducer-2 in enteric bacteria. ACS Chem Biol 2: 128-136. PubMed

Tu KC, Bassler BL. (2007) Multiple small RNAs act additively to integrate sensory information and control quorum sensing in Vibrio harveyi. Genes Dev 21: 221-233. PubMed

Lenz DH, Bassler BL. (2007) The small nucleoid protein Fis is involved in Vibrio cholerae quorum sensing. Mol Microbiol 63: 859-871. [PubMed]

Waters CM and Bassler BL. (2006) The Vibrio harveyi quorum-sensing system uses shared regulatory components to discriminate between multiple autoinducers. Genes Dev 20: 2754-2767. PubMed

Neiditch MB, Federle MJ, Pompeani AJ, Kelly RC, Swem DL, Jeffrey PD, Bassler BL, Hughson FM. (2006) Ligand-induced asymmetry in histidine sensor kinase complex regulates quorum sensing. Cell 126: 1095-1108. PubMed

Bassler BL. (2006) Cell-to-cell communication in bacteria: a chemical discourse. Harvey Lect. 2004-2005 100: 123-142. PubMed

Bassler BL, Losick R. (2006) Bacterially speaking. Cell 125: 237-246. PubMed

Camilli A, Bassler BL. (2006) Bacterial small-molecule signaling pathways. Science 311: 1113-1116. PubMed

Xavier KB, Bassler BL. (2005) Regulation of uptake and processing of the quorum-sensing autoinducer AI-2 in Escherichia coli. J Bacteriol 187: 238-248. PubMed

Xavier KB, Bassler BL. (2005) Interference with AI-2-mediated bacterial cell-cell communication. Nature 437: 750-753. PubMed

Waters CM, Bassler BL. (2005) Quorum sensing: cell-to-cell communication in bacteria. Annu Rev Cell Dev Biol 21: 319-346. PubMed

Ulrich DL, Kojetin D, Bassler BL, Cavanagh J, Loria JP. (2005) Solution structure and dynamics of LuxU from Vibrio harveyi, a phosphotransferase protein involved in bacterial quorum sensing. J Mol Biol 347: 297-307. PubMed

Semmelhack MF, Campagna SR, Federle MJ and Bassler BL (2005). An expeditious synthesis of DPD and boron binding studies. Org Lett 7: 569-572. PubMed

Neiditch MB, Federle MJ, Miller ST, Bassler BL and Hughson FM (2005). Regulation of LuxPQ receptor activity by the quorum-sensing signal autoinducer-2. Mol Cell 18: 507-518. PubMed

Lenz DH, Miller MB, Zhu J, Kulkarni RV and Bassler BL (2005). CsrA and three redundant small RNAs regulate quorum sensing in Vibrio cholerae. Mol Microbiol 58: 1186-1202. PubMed

Ulrich DL, Thompson R, Bassler B, Cavanagh J and Loria JP (2004). 1H, 15N, and 13C chemical shift assignments of the Vibrio harveyi histidine phosphotransferase protein LuxU. J Biomol NMR 29: 551-552. PubMed

Semmelhack MF, Campagna SR, Hwa C, Federle MJ and Bassler BL (2004). Boron binding with the quorum sensing signal AI-2 and analogues. Org Lett 6: 2635-2637. PubMed

Miller ST, Xavier KB, Campagna SR, Taga ME, Semmelhack MF, et al. (2004). Salmonella typhimurium recognizes a chemically distinct form of the bacterial quorum-sensing signal AI-2. Mol Cell 15: 677-687. PubMed

Lenz DH, Mok KC, Lilley BN, Kulkarni RV, Wingreen NS, et al. (2004). The small RNA chaperone Hfq and multiple small RNAs control quorum sensing in Vibrio harveyi and Vibrio cholerae. Cell 118: 69-82. PubMed

Henke JM and Bassler BL (2004). Quorum sensing regulates type III secretion in Vibrio harveyi and Vibrio parahaemolyticus. J Bacteriol 186: 3794-3805. PubMed

Henke JM and Bassler BL (2004). Three parallel quorum-sensing systems regulate gene expression in Vibrio harveyi. J Bacteriol 186: 6902-6914. PubMed

Henke JM and Bassler BL (2004). Bacterial social engagements. Trends Cell Biol 14: 648-656. PubMed

Zhao G, Wan W, Mansouri S, Alfaro JF, Bassler BL, et al. (2003). Chemical synthesis of S-ribosyl-L-homocysteine and activity assay as a LuxS substrate. Bioorg Med Chem Lett 13: 3897-3900. PubMed

Xavier KB and Bassler BL (2003). LuxS quorum sensing: more than just a numbers game. Curr Opin Microbiol 6: 191-197. PubMed

Taga ME, Miller ST and Bassler BL (2003). Lsr-mediated transport and processing of AI-2 in Salmonella typhimurium. Mol Microbiol 50: 1411-1427. PubMed

Taga ME and Bassler BL (2003). Chemical communication among bacteria. Proc Natl Acad Sci USA 100 Suppl 2: 14549-14554. PubMed

Mok KC, Wingreen NS and Bassler BL (2003). Vibrio harveyi quorum sensing: a coincidence detector for two autoinducers controls gene expression. Embo J 22: 870-881. PubMed

Hammer BK and Bassler BL (2003). Quorum sensing controls biofilm formation in Vibrio cholerae. Mol Microbiol 50: 101-104. PubMed

Federle MJ and Bassler BL (2003). Interspecies communication in bacteria. J Clin Invest 112: 1291-1299. PubMed

Zhu J, Miller MB, Vance RE, Dziejman M, Bassler BL, et al. (2002). Quorum-sensing regulators control virulence gene expression in Vibrio cholerae. Proc Natl Acad Sci USA 99: 3129-3134. PubMed

Winans SC and Bassler BL (2002). Mob psychology. J Bacteriol 184: 873-883. PubMed

Miller MB, Skorupski K, Lenz DH, Taylor RK and Bassler BL (2002). Parallel quorum sensing systems converge to regulate virulence in Vibrio cholerae. Cell 110: 303-314. PubMed

Chen X, Schauder S, Potier N, Van Dorsselaer A, Pelczer I, et al. (2002). Structural identification of a bacterial quorum-sensing signal containing boron. Nature 415: 545-549. PubMed

Bassler BL (2002). Small talk. Cell-to-cell communication in bacteria. Cell 109: 421-424. PubMed

Taga ME, Semmelhack JL and Bassler BL (2001). The LuxS-dependent autoinducer AI-2 controls the expression of an ABC transporter that functions in AI-2 uptake in Salmonella typhimurium. Mol Microbiol 42: 777-793. PubMed

Schauder S, Shokat K, Surette MG and Bassler BL (2001). The LuxS family of bacterial autoinducers: biosynthesis of a novel quorum-sensing signal molecule. Mol Microbiol 41: 463-476. PubMed

Schauder S and Bassler BL (2001). The languages of bacteria. Genes Dev 15: 1468-1480. PubMed

Miller MB and Bassler BL (2001). Quorum sensing in bacteria. Annu Rev Microbiol 55: 165-199. PubMed

Lilley BN and Bassler BL (2000). Regulation of quorum sensing in Vibrio harveyi by LuxO and sigma-54. Mol Microbiol 36: 940-954. PubMed

Joyce EA, Bassler BL and Wright A (2000). Evidence for a signaling system in Helicobacter pylori: detection of a luxS-encoded autoinducer. J Bacteriol 182: 3638-3643. PubMed

Freeman JA, Lilley BN and Bassler BL (2000). A genetic analysis of the functions of LuxN: a two-component hybrid sensor kinase that regulates quorum sensing in Vibrio harveyi. Mol Microbiol 35: 139-149. PubMed

Surette MG, Miller MB and Bassler BL (1999). Quorum sensing in Escherichia coli, Salmonella typhimurium, and Vibrio harveyi: a new family of genes responsible for autoinducer production. Proc Natl Acad Sci USA 96: 1639-1644. PubMed

Surette MG and Bassler BL (1999). Regulation of autoinducer production in Salmonella typhimurium. Mol Microbiol 31: 585-595. PubMed

Freeman JA and Bassler BL (1999). Sequence and function of LuxU: a two-component phosphorelay protein that regulates quorum sensing in Vibrio harveyi. J Bacteriol 181: 899-906. PubMed

Freeman JA and Bassler BL (1999). A genetic analysis of the function of LuxO, a two-component response regulator involved in quorum sensing in Vibrio harveyi. Mol Microbiol 31: 665-677. PubMed

Bassler BL (1999). How bacteria talk to each other: regulation of gene expression by quorum sensing. Curr Opin Microbiol 2: 582-587. PubMed

Surette MG and Bassler BL (1998). Quorum sensing in Escherichia coli and Salmonella typhimurium. Proc Natl Acad Sci USA 95: 7046-7050. PubMed

Bassler BL, Greenberg EP and Stevens AM (1997). Cross-species induction of luminescence in the quorum-sensing bacterium Vibrio harveyi. J Bacteriol 179: 4043-4045. PubMed

Bassler BL, Wright M and Silverman MR (1994). Sequence and function of LuxO, a negative regulator of luminescence in Vibrio harveyi. Mol Microbiol 12: 403-412. PubMed

Bassler BL, Wright M and Silverman MR (1994). Multiple signalling systems controlling expression of luminescence in Vibrio harveyi: sequence and function of genes encoding a second sensory pathway. Mol Microbiol 13: 273-286. PubMed

Yu C, Bassler BL and Roseman S (1993). Chemotaxis of the marine bacterium Vibrio furnissii to sugars. A potential mechanism for initiating the chitin catabolic cascade. J Biol Chem 268: 9405-9409. PubMed

Bassler BL, Wright M, Showalter RE and Silverman MR (1993). Intercellular signalling in Vibrio harveyi: sequence and function of genes regulating expression of luminescence. Mol Microbiol 9: 773-786. PubMed

Yu C, Lee AM, Bassler BL and Roseman S (1991). Chitin utilization by marine bacteria. A physiological function for bacterial adhesion to immobilized carbohydrates. J Biol Chem 266: 24260-24267. PubMed

Bassler BL, Yu C, Lee YC and Roseman S (1991). Chitin utilization by marine bacteria. Degradation and catabolism of chitin oligosaccharides by Vibrio furnissii. J Biol Chem 266: 24276-24286. PubMed

Bassler BL, Gibbons PJ, Yu C and Roseman S (1991). Chitin utilization by marine bacteria. Chemotaxis to chitin oligosaccharides by Vibrio furnissii. J Biol Chem 266: 24268-24275. PubMed

Bassler B, Gibbons P and Roseman S (1989). Chemotaxis to chitin oligosaccharides by Vibrio furnissii, a chitinivorous marine bacterium. Biochem Biophys Res Commun 161: 1172-1176. PubMed

Hallenbeck PC, Vimr ER, Yu F, Bassler B and Troy FA (1987). Purification and properties of a bacteriophage-induced endo-N-acetylneuraminidase specific for poly-alpha-2,8-sialosyl carbohydrate units. J Biol Chem 262: 3553-3561. PubMed


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