Cyclic Peptides that Govern Signal Transduction Pathways: From Prokaryotes to Multi-Cellular Organisms

Abstract

Cyclic peptide scaffolds are key components of signal transduction pathways in both prokaryotic and eukaryotic organisms since they act as chemical messengers that activate or inhibit specific cognate receptors. In prokaryotic organisms these peptides are utilized in non-essential pathways, such as quorum sensing, that are responsible for virulence and pathogenicity. In the more evolved eukaryotic systems, cyclic peptide hormones play a key role in the regulation of the overall function of multicellular organisms, mainly through the endocrine system. This review will highlight several prokaryote and eukaryote systems that use cyclic peptides as their primary signals and the potential associated with utilizing these scaffolds for the discovery of novel therapeutics for a wide range of diseases and illnesses.

Development of a Dominant Negative Competence‐Stimulating Peptide (dnCSP) that Attenuates Streptococcus pneumoniae Infectivity in a Mouse Model of Acute Pneumonia

“…The QS circuitry is also involved in virulence factor production and biofilm formation, thus making the competence regulon an attractive target for attenuating pneumococcus infections, while at the same time, preventing the acquisition of antibiotic resistance genes. Moreover, because QS is not essential for bacterial growth, it has attracted significant attention over the past two decades as a potential anti‐infective target that places minimal selective pressure for the development of resistance against a multitude of bacterial pathogens . Two main CSP variants, CSP1 and CSP2, have been identified in pneumococcus, leading to two distinct pherotypes being classified (Figure ).…”

Exogenous Protein as an Environmental Stimuli of Biofilm Formation in Select Bacterial Strains

“…Protein and/or peptides in the concentrations ranges where we have detected enhanced biofilm formation would saturate protein binding sites on the cell surface. Some of these sites, as in the case of Enteroco ccus (34, 49, 50), are linked to two-component regulatory systems, hence exogenous protein may be an environmental trigger for biofilm formation.…”

Progress Overview of Bacterial Two-Component Regulatory Systems as Potential Targets for Antimicrobial Chemotherapy

“…AIP analogues of some other Gram-positive pathogens, such as S. epidermidis and E. faecalis , were also reported [ 67 , 68 ]. An overview of AIPs and their antagonists was recently reviewed [ 69 ].…”

“… WalK Dimerization [ 59 , 60 ] AIP analogues AgrC, ComD, FsrC etc. AIP sensing [ 63 , 64 , 65 , 66 , 67 , 68 , 69 ] DevR mimetic peptides DevS Auto-phosphorylation [ 71 ] Response regulator inhibitors Lactoferricin B BasR, CreB Phosphorylation [ 76 ] Rhein PhoP Phosphorylation [ 79 ] Nitrophenyl derivative NarL Phosphorylation [ 72 ] Alkyl imidazoles AlgR1 Binding to target DNAs [ 17 ] Walrycin WalR Dimerization …”