Exploring the chemical space of quorum sensing peptides

Abstract

Quorum sensing peptides are signalling molecules that are produced by mainly gram-positive bacteria. These peptides can exert different effects, ranging from intra- and interspecies bacterial virulence to bacterial-host interactions. To better comprehend these functional differences, we explored their chemical space, bacterial species distribution and receptor-binding properties using multivariate data analyses, with information obtained from the Quorumpeps database. The quorum sensing peptides can be categorized into three main clusters, which, in turn, can be divided into several subclusters: the classification is based on characteristic chemical properties, including peptide size/compactness, hydrophilicity/lipophilicity, cyclization and the presence of (unnatural) S-containing and aromatic amino acids. Most of the bacterial species synthesize peptides located into one cluster. However, some Streptococcus, Stapylococcus, Clostridium, Bacillus and Lactobacillus species produce peptides that are distributed over more than one cluster, with the quorum sensing peptides of Bacillus subtilis even occupying the total peptide space. The AgrC, FsrC and LamC receptors are only activated by cyclic (thio)lacton or lactam quorum sensing peptides, while the lipophilic isoprenyl-modified peptides solely bind the ComP receptor in Bacillus species.

Quorum Sensing Peptides Selectively Penetrate the Blood-Brain Barrier

“…The clustering results of the quorum sensing peptides are given in Fig 1 : three main, chemically diverse clusters can be distinguished [ 27 ]. One peptide from each cluster was selected, resulting in three chemically diverse molecules, i .…”

“…a . the WHIM size index and the Wiener W index [ 27 ]. As BBB permeability generally increases with lipophilicity, i .…”

“…PhrANTH2 < BIP-2 < PhrCACET1, our findings are consistent with current physicochemical explanations of BBB transport characteristics of peptides [ 51 ]. When we analyze the clustering results of all Quorumpeps peptides (n = 231, Fig 1 ) [ 26 , 27 ] and select the peptides with a comparable lipophilicity as PhrCACET1 ( i . e .…”

“…After removal of the constant descriptors, and correction for molecular weight, a final dataset of 1468 descriptors was retained. Multivariate data-analysis on this resulting 231×1468 data-matrix was performed using Principal Component Analysis (PCA) with SIMCA-P+ 12.0 (Umetrics, Sweden) and different clusters identified [ 27 ]. Finally, three chemically diverse quorum sensing peptides were selected to investigate their brain permeability characteristics.…”

Analysis of iodinated quorum sensing peptides by LC–UV/ESI ion trap mass spectrometry

“…In this study, five QSP were iodinated using different techniques and their analytical characterization was investigated. These five peptides are situated in three different clusters (clusters 2A, 2B and 3A) of the quorum sensing peptide chemical space [24] and are involved in mediating cell death (Q19) [25] , plasmid transfer (Q132, Q184) [26] , [27] , expressing virulence factors (Q164) [28] and inhibition of Rap phosphatases (Q206) [29] . Q19 and Q164 bind a membrane associated receptor while Q132, Q184 and Q206 are internalized and bind to a cytoplasmic receptor.…”