Michael meijler.jpg
Ph.D.:
Weizmann Institute of Science, Israel
Post-doctorate: The Scripps Research Institute, USA
Position: Associate Professor
Department of Chemistry, Faculty of Natural Sciences
E-mail: meijler@bgu.ac.il

 

Chemical biology of bacterial communication

 

 

   

  • Background

Cell-to-cell communication is used by single-cell organisms to coordinate their behavior and function in such a way that they can adapt to changing environments and possibly compete with multicellular organisms. This phenomenon has been termed “quorum sensing” (QS). Examples of QS-controlled behaviors are biofilm formation, virulence factor expression, antibiotic production and bioluminescence. These processes are beneficial to a bacterial population only when they are carried out in a coordinated fashion.

 

  • Current research

Quorum Sensing
An important focus of my group’s research is the study of bacterial intra- and interspecies signaling. Cell-to-cell communication is used by single-cell organisms to coordinate their behavior and function in such a way that they can adapt to changing environments and possibly compete with multicellular organisms. This phenomenon has been termed “quorum sensing” (QS). Examples of QS-controlled behaviors are biofilm formation, virulence factor expression, antibiotic production and bioluminescence. These processes are beneficial to a bacterial population only when they are carried out in a coordinated fashion. Quorum sensing systems exist in both grampositive and -negative bacteria and a variety of oligopeptides and N-acyl-homoserine lactones have been identified as QS molecules. However, many QS systems have not been characterized fully, thus we will attempt to clarify the role of various QS molecules in bacterial
signaling (in species such as Pseudomonas aeruginosa, Salmonella typhimurium, Helicobacter pylori). Through the synthesis and evaluation of QS molecules and potential antagonists we will develop methodologies to study a wide variety of newly discovered and undiscovered QS molecules. Currently, as part of two different studies to design QS antagonists of P. aeruginosa, we have synthesized several highly active covalent and non-covalent QS inhibitors.

Bacterial-Eukaryotic Interkingdom Signaling
Recent reports have shown that several QS molecules can also have a direct effect on eukaryotes. Diverse eukaryotes have been found to react strongly to the presence of these compounds. My group currently examines the hypothesis that diverse eukaryotic species have developed mechanisms to react to the presence of specific bacterial QS molecules in a receptor-mediated fashion. We perform focused experiments designed to provide greater insight into the primary molecular mechanism of QS molecule induced effects on mammals, fungi and nematodes. Identification of specific QSM receptors in eukaryotes will allow us to further understand the complex mechanisms of coexistence and the evolution of coexistence between prokaryotes and eukaryotes. Ultimately insights obtained from these experiments could lead to: a) new approaches for the treatment of P. aeruginosa infections, most notably in the clinical setting of cystic fibrosis, as well as to potential new drugs for the treatment of autoimmune diseases; b) an increased  understanding of the general principles that guide the evolution of symbiotic relationships between competing species; c) the development of an integrated platform that will enable the discovery of unknown receptors for small hydrophobic bioactive compounds.

 
  • Publications

Amara N., Mashiach R., Amara D., Krief P., Spieser S.A., Bottomley M.J., Aharoni A. and Meijler M.M. (2009). Covalent Inhibition of Bacterial Quorum Sensing. J. Am. Chem. Soc. 131:10610-10619.

Dubinsky L., Jarosz L.M., Amara N., Krief P., Kravchenko V., Krom B.P. and Meijler M.M. (2009). Synthesis and validation of a probe to identify quorum sensing receptors. Chem. Commun. 47:7378-7380.

Rayo J., Amara N., Krief P. and Meijler M.M. (2011). Live cell labeling of native intracellular bacterial receptors using aniline-catalyzed oxime ligation. J. Am. Chem. Soc. 133:7469-7475.

Ganin H., Danin-Poleg Y., Kashi Y. and Meijler M.M. (2012). Vibrio cholerae Autoinducer CAI-1 Interferes with Pseudomonas aeruginosa Quorum Sensing and Inhibits its Growth. ACS Chem. Biol. 7:659-665.

Dubinsky L., Delago A., Amara N., Krief P., Rayo J., Zor T., Kravchenko V.V. and Meijler M.M. (2013). Species selective diazirine positioning in tag-free photoactive quorum sensing probes. Chem. Commun. 49:5826-5828.

Mandabi A., Ganin H., Rayo J. and Meijler M.M. (2013). Karrikins from Plant Smoke Modulate Bacterial Quorum Sensing. Chem. Commun. 50(40):5322-5325.