Structural insights into streptococcal competence regulation by the cell-to-cell communication system ComRS

A. Talagas, L. Fontaine, L. Ledesma-Garcia, J. Mignolet, I. Li de la Sierra-Gallay, N. Lazar, M. Aumont-Nicaise, M. J. Federle, G. Prehna, P. Hols, and S. Nessler, PLoS Pathog, 12 (2016)

Speaker: Tsai-Yu Wu (吳彩瑜)                                             Time: 14:00~15:00, Mar. 08, 2017

Commentator: Dr. Wen-Yih Jeng (鄭文義老師)          Place: Room 601

Abstract

Cell-to-cell communication relied on the production and detection of signaling peptide in Gram-positive bacteria, and this phenomenon was known as quorum sensing (QS). QS is a type of regulatory process correlated to population density. By sensing the concentration of extracellular pheromones, this process allows bacteria to increase the target gene expression and escape from the attack from the environment¹. In Gram-positive bacteria, the extracellular peptides were recognized by cytoplasmic effectors, the RNPP (Rap, NprR, PrgX and PlcR) protein family. These proteins were characterized by a tetratricopeptide-repeat (TPR)-type peptide-binding domain, and except for Rap protein, also contain an N-terminal HTH-type DNA-binding domain². These effector proteins display a transcriptional activity. Recently, transcriptional regulators Rgg have been included in RNPP family, and there were two sub-clusters been defined. The small hydrophobic peptides (SHP)-associated Rgg and ComR regulators³. In streptococcal species, the competence development was regulated by ComR regulators, and they were activated by ComS signaling peptides, those matured form called comX/sigX-inducing peptide (XIP). Previous studies showed that inhibiting competence was effective in drug design. However, the mechanism of ComR regulators were still unclear. In this study, the authors solved the crystal structure of ComR from Streptococcus thermophiles and the ComR/XIP/DNA complex structure. Combined with mutagenesis studies and in vivo assays to investigate the molecular mechanism of ComR regulation mode, the authors found that the apo-form of ComR hold the sequestered HTH domain and exist as an inactive monomeric state, while XIP-binding induced conformational change of ComR regulator to release the HTH domain for DNA binding and combined to an active dimer. More importantly, identification of the specific residues for XIP and ComR interaction is crucial for the antagonists search to control gene transfer among streptococci. These results may provide a different insight into design the antimicrobial drugs.

References

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2.  Aravind, L., Anantharaman, V., Balaji, S., Babu, M.M. & Iyer, L.M. The many faces of the helix-turn-helix domain: transcription regulation and beyond. FEMS microbiology reviews 29, 231-262 (2005).

3. Fleuchot, B., et al. Rgg proteins associated with internalized small hydrophobic peptides: a new quorum-sensing mechanism in streptococci. Molecular microbiology 80, 1102-1119 (2011).