Biological activity and identification of a peptide inhibitor of LuxS from Streptococcus suis serotype 2.
The virulence of bacterial communities may be regulated by mechanisms involving the synthesis of the quorum-sensing signal autoinducer 2 (AI-2), which allows both intra- and interspecies communication. AI-2 is produced in bacteria that express the gene luxS. In the present study, expressed and purified LuxS from Streptococcus suis serotype 2 (SS2) was used to catalyze the substrate S-ribosylhomocysteine in a reaction that leads to the production of AI-2. The biological activity of the in vitro synthesized AI-2 was demonstrated in a Vibrio harveyi strain BB170 bioassay; real-time PCR results showed that biosynthesis of AI-2 can increase the virulence of SS2. Phage-encoded peptides that specifically interact with the LuxS enzyme were selected following three rounds of phage display. One such peptide inhibitor (TNRHNPHHLHHV) of LuxS was shown to partially inhibit the activity of the enzyme. Furthermore, 14 peptides containing the consensus sequence HSIR showed high affinity with LuxS. The selected and characterized specific inhibitor as well as the high-affinity ligands may facilitate the identification of new vaccination targets, opening up new approaches to the development of therapeutic drugs.
Han
Xiangan
X
Key Laboratory of Animal Disease Diagnostics and Immunology, Ministry of Agriculture, Nanjing Agricultural University, Nanjing, China.
Lu
Chengping
C
D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000302:isolation & purification; D001681:Biological Assay; D013437:Carbon-Sulfur Lyases / Q000037:antagonists & inhibitors* / Q000302:isolation & purification; D004791:Enzyme Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D020869:Gene Expression Profiling; D006710:Homocysteine / Q000031:analogs & derivatives / Q000378:metabolism; D006714:Homoserine / Q000031:analogs & derivatives / Q000378:metabolism; D006801:Humans; D007783:Lactones / Q000378:metabolism; D008969:Molecular Sequence Data; D019151:Peptide Library; D010455:Peptides / Q000302:isolation & purification / Q000494:pharmacology*; D053038:Quorum Sensing; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017011:Streptococcus suis / Q000201:enzymology* / Q000472:pathogenicity; D014733:Vibrio / Q000502:physiology; D037521:Virulence Factors / Q000096:biosynthesis
D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D007783:Lactones; C091088:N-octanoylhomoserine lactone; D019151:Peptide Library; D010455:Peptides; C487472:S-ribosyl-L-homocysteine; D037521:Virulence Factors; D006710:Homocysteine; D006714:Homoserine; D013437:Carbon-Sulfur Lyases; C117753:LuxS protein, Bacteria