A system of stimuli and response correlated to population density is called quorum sensing (QS). Bacteria use QS circuits via autoinducers to regulate microbial behaviors and processes including virulence, biofilm formation, and bioluminescence. Autoinducer-2, or its direct precursor (4S)-4,5-dihydroxy-2,3-pentanedione (DPD), is utilized by both Gram-positive and negative bacteria. It has thus been proposed as the universal QS molecule. However, a definitive link between DPD signal, receptor, and bacterial infectivity/survival is still lacking.
Kim D. Janda and colleagues, Scripps Research Institute, La Jolla, CA, USA, found that DPD is a glycating agent. This results, e.g., in altered functions of viral DNA and in reduced antibiotic potency when DPD reacts with peptide antibiotics. Probing further, the researchers developed a protein-labeling method that enabled the identification of previously undocumented targets/receptors of DPD. The results showed that in a native sample of whole-cell lysate (S. typhimurium strain 14028), 63 proteins gave positive hits for DPD glycation.
Currently, the researchers are investigating the downstream effects of DPD glycation as it relates to QS and microbial pathology, to find out if DPD-induced modifications underlie bacterial pathogenicity.
- Glycation Reactivity of a Quorum-Sensing Signaling Molecule,
Kyoji Tsuchikama, Major Gooyit, Tyler L. Harris, Jie Zhu, Daniel Globisch, Gunnar F. Kaufmann, Kim D. Janda,
Angew. Chem. Int. Ed. 2016, 55, 4002–4006.