Quorum sensing is a complex, collective behavior displayed by a variety of bacterial species when the cell population density exceeds the critical value. Examples of processes modulated by quorum sensing are the development of genetic competence, conjugative plasmid transfer, sporulation and cell differentiation, biofilm formation, virulence response, production of antibiotics, antimicrobial peptides and toxins, and bioluminescence. Collective behavior in quorum sensing can result in the formation of biofilms, highly organized and spatially structured bacterial colonies encased in polysaccharide gels. The U.S. Centers for Disease Control has estimated that biofilms cause 65 percent of infections in the developed world. Biofilm formation plagues the use of intravenous, endotracheal and urinary tubes, surgical sutures, catheters and contact lenses. Biofilms can display very sophisticated temporal and spatial self-organizing behavior characteristic of complex systems. Therefore quantitative understanding of the mechanisms underlying quorum sensing is essential for combating developing infectious diseases in clinic. Here we propose to investigate adaptive properties of quorum sensing both theoretically, by construction of computational model of randomly seeded interacting cells and experimentally, by investigating single cell and population responses in an experimental model of quorums sensing: Vibrio fischeri. In particular, we will investigate the hypothesis that biphasic regulation of diffusible autoinducer production by individual cells on the local autoinducer concentration makes quorum sensing robust to global and local variations in cell density. In addition, we will verify the prediction that biphasic nature of autoinducer autoregulation allows cells to reduce high metabolic load necessary to maintain high level quorum response. These hypotheses suggest high degree of adaptability and robustness in quorum sensing response. The model proposed is an example of an algorithmic, bottom-up approach that allows to take the natural noisiness and variability into account in the analysis of experimental data. As a part of the proposal we will develop a novel method for analysis of V. fischeri quorum sensing at very high cell densities, normally not allowed in the batch liquid cell culture. Following verification, the model development will be extended to include multi-species interaction in biofilm formation and analysis of biofilm structure in light of quorum sensing. ? ? ?

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Microbial Physiology and Genetics Subcommittee 2 (MBC)
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Deatherage, James F
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Johns Hopkins University
Biomedical Engineering
Schools of Medicine
United States
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Williams, Joshua W; Ritter, A L; Stevens, Ann M (2012) CsrA modulates luxR transcript levels in Vibrio fischeri. FEMS Microbiol Lett 329:28-35
Schu, Daniel J; Ramachandran, Revathy; Geissinger, Jared S et al. (2011) Probing the impact of ligand binding on the acyl-homoserine lactone-hindered transcription factor EsaR of Pantoea stewartii subsp. stewartii. J Bacteriol 193:6315-22
Williams, Joshua W; Cui, Xiaohui; Levchenko, Andre et al. (2008) Robust and sensitive control of a quorum-sensing circuit by two interlocked feedback loops. Mol Syst Biol 4:234
Antunes, Luis Caetano M; Schaefer, Amy L; Ferreira, Rosana B R et al. (2007) Transcriptome analysis of the Vibrio fischeri LuxR-LuxI regulon. J Bacteriol 189:8387-91
Cho, HoJung; Jonsson, Henrik; Campbell, Kyle et al. (2007) Self-organization in high-density bacterial colonies: efficient crowd control. PLoS Biol 5:e302
Qin, Nan; Callahan, Sean M; Dunlap, Paul V et al. (2007) Analysis of LuxR regulon gene expression during quorum sensing in Vibrio fischeri. J Bacteriol 189:4127-34
Kulkarni, Prajna R; Cui, Xiaohui; Williams, Joshua W et al. (2006) Prediction of CsrA-regulating small RNAs in bacteria and their experimental verification in Vibrio fischeri. Nucleic Acids Res 34:3361-9
Groisman, Alex; Lobo, Caroline; Cho, HoJung et al. (2005) A microfluidic chemostat for experiments with bacterial and yeast cells. Nat Methods 2:685-9