A Method for Structure–Activity Analysis of Quorum-Sensing Signaling Peptides from Naturally Transformable Streptococci

Xiaolin Tian,Nadine Livingstone,David L Jakeman,Tianlei Liu,Yung-Hua Li,Raymond T Syvitski

doi:10.1007/s12575-009-9009-9

Xiaolin Tian, Nadine Livingstone + Show 4 more

Open Access

https://doi.org/10.1007/s12575-009-9009-9

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Abstract

Many species of streptococci secrete and use a competence-stimulating peptide (CSP) to initiate quorum sensing for induction of genetic competence, bacteriocin production, and other activities. These signaling molecules are small, unmodified peptides that induce powerful strain-specific activity at nano-molar concentrations. This feature has provided an excellent opportunity to explore their structure–function relationships. However, CSP variants have also been identified in many species, and each specifically activates its cognate receptor. How such minor changes dramatically affect the specificity of these peptides remains unclear. Structure–activity analysis of these peptides may provide clues for understanding the specificity of signaling peptide–receptor interactions. Here, we use the Streptococcus mutans CSP as an example to describe methods of analyzing its structure–activity relationship. The methods described here may provide a platform for studying quorum-sensing signaling peptides of other naturally transformable streptococci.

Highlights

Natural genetic transformation is a process by which bacteria are able to take up and integrate exogenous free DNA from their environment [1, 2]
Using circular dichroism (CD) and nuclear magnetic resonance (NMR) spectroscopy, we have determined the three-dimensional structures of two signaling peptides, UA159sp from S. mutans UA159 and a C-terminally truncated peptide TPC3 from JH1005 defective in genetic competence [10]
Our work suggests that the quorum-sensing signaling peptides from S. mutans, probably from other naturally transformable streptococci, fall into the FXXFF motif family, a general protein–protein interaction motif, where the interaction is made through a hydrophobic face formed by the hydrophobic residues packed into a hydrophobic pocket of the receptor [11, 12, 26]

Summary

Introduction

Natural genetic transformation is a process by which bacteria are able to take up and integrate exogenous free DNA from their environment [1, 2]. This process enables the recipient organisms to acquire novel genes, thereby promoting the emergence of antibiotic resistance, genetic variation, and rapid evolution of virulence factors [1,2,3,4]. Activation of quorum sensing for genetic competence and other coordinated activities in these species requires at least six gene products encoded by comCDE, comAB, and comX (Fig. 1). In contrast to S. mutans, Streptococcus pneumoniae requires two separate signaling systems, the ComCDE and BlpRH, to regulate genetic competence and bacteriocin production [8]

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