Functional selection of a type IV pili-binding peptide that specifically inhibits Salmonella Typhi adhesion to/invasion of human monocytic cells.
Salmonella enterica serovar Typhi (S. Typhi) is an important pathogen which infects humans exclusively and causes typhoid or enteric fever. Recently it has been discovered that type IVB pili, encoded by the S. Typhi pil operon located in the major pathogenicity island, may be important in the pathogenesis of epidemic enteric fever. To further investigate the roles of type IVB pili of S. Typhi, a 12-mer peptide (RQERSSLSKPVV), binding to the structural protein PilS of the type IVB pili of S. Typhi, was isolated with a ribosome display system. This peptide was designated as peptide R. We found that peptide R inhibited adhesion to/invasion of human monocytic THP-1 cells by piliated S. Typhi bacteria, but had no effects on nonpiliated S. Typhi bacteria. A random 12-mer peptide, of size and solubility equal to peptide R, served as a control on the specificity of peptide R. The specific interaction and binding equilibrium between the 12-mer peptide R and PilS protein was determined by isothermal titration calorimetry (ITC) and a binding constant Ka determined to be between 0.4 x 10(5) and 2.2 x 10(5)L mol(-1). Our findings suggest that the type IV pili-binding peptide R holds potential as an antibacterial peptide effective against S. Typhi infections, both in terms of prevention and therapeutic treatment. The data further provide insights into the understanding of the pathogenic roles of the type IVB pili of S. Typhi.
Wu
Hong-Yan
HY
Department of Immunology, Wuhan University School of Medicine, Donghu Road 115#, Wuhan 430071, PR China.
Zhang
Xiao-Lian
XL
Pan
Qin
Q
Wu
Jianguo
J
D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D001422:Bacterial Adhesion / Q000187:drug effects; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D002460:Cell Line; D036781:Fimbriae Proteins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D010861:Fimbriae, Bacterial / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D009000:Monocytes / Q000382:microbiology; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D011485:Protein Binding; D012485:Salmonella typhi / Q000737:chemistry* / Q000472:pathogenicity; D014435:Typhoid Fever / Q000188:drug therapy / Q000382:microbiology
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D009842:Oligopeptides; C508415:type IVB pili, Salmonella typhi; D036781:Fimbriae Proteins