Histone H1 Proteins Act As Receptors for the 987P Fimbriae of Enterotoxigenic Escherichia coli

Abstract

The tip adhesin FasG of the 987P fimbriae of enterotoxigenic Escherichia coli mediates two distinct adhesive interactions with brush border molecules of the intestinal epithelial cells of neonatal piglets. First, FasG attaches strongly to sulfatide with hydroxylated fatty acyl chains. This interaction involves lysine 117 and other lysine residues of FasG. Second, FasG recognizes specific intestinal brush border proteins that migrate on a sodium-dodecyl sulfate-polyacrylamide gel like a distinct set of 32-35-kDa proteins, as shown by ligand blotting assays. The protein sequence of high performance liquid chromatography-purified tryptic fragments of the major protein band matched sequences of human and murine histone H1 proteins. Porcine histone H1 proteins isolated from piglet intestinal epithelial cells demonstrated the same SDS-PAGE migration pattern and 987P binding properties as the 987P-specific protein receptors from porcine intestinal brush borders. Binding was dose-dependent and shown to be specific in adhesion inhibition and gel migration shift assays. Moreover, mapping of the histone H1 binding domain suggested that it is located in their lysine-rich C-terminal domains. Histone H1 molecules were visualized on the microvilli of intestinal epithelial cells by immunohistochemistry and electron microscopy. Taken together these results indicated that the intestinal protein receptors for 987P are histone H1 proteins. It is suggested that histones are released into the intestinal lumen by the high turnover of the intestinal epithelium. Their strong cationic properties can explain their association with the negatively charged brush border surfaces. There, the histone H1 molecules stabilize the sulfatide-fimbriae interaction by simultaneously binding to the membrane and to 987P. Enterotoxigenic Escherichia coli (ETEC)1 cause diarrhea in mammals by expressing at least one type of enteroadhesive fimbria and one type of enterotoxin. By adhering to intestinal epithelial cells, localized multiplication of an ETEC strain can progress to mucosal surface colonization and concomitant effective enterotoxin delivery. This was illustrated with hostspecific ETEC strains in both animals and human volunteers (1-5). ETEC are the most important etiologic agents of both neonatal and postweaning diarrhea in pigs (6, 7). 987P-fimbriated ETEC cause diarrhea in neonatal piglets in the United States (8), Europe (9, 10), Asia (11-15), and Central and South America (16 -18). In addition to this widespread distribution, the recent identification of human ETEC strains with 987P-like fimbriae (19, 20) on various continents highlights the evolutionary adaptability of these fimbriae (21).The 987P fimbria consists of the helical arrangement of protein subunits along a filamentous axis (22,23). It is a heteropolymeric structure that is made up of one major subunit, FasA, and two minor subunits, FasF and FasG (24). Fimbriae are not produced in the absence of any of these subunits (25). Electron microscopy and export studies indicated that FasG ...

An Adhesin-Like Protein, Lam29, fromLactobacillus mucosaeME-340 Binds to Histone H3 and Blood Group Antigens in Human Colonic Mucus

“…19) In a recent study, however, histones were found at the cell surface on monocytes, lymphocytes, and epithelial cells. [20][21][22][23] Rose et al reported that detached villus epithelial cells released histone H1 into the intestinal lumen by rapid turnover and found it had antimicrobial activity against microorganisms. 24) The mucosal surfaces of the human intestine contain negatively charged molecules, including sialic acid and sulfate groups.…”

“…In the former case, the binding of surfaceassociated histone-like protein (HlpA) from Streptococcus gallolyticus to colon adenocarcinoma cells 29) and the binding of Hlp/LBP from Mycobacterium leprae to the extracellular matrix, 30) and in the latter case, the adhesion of 987P fimbriae from enterotoxigenic E. coli to histone H1 receptor 23) were reported. This indicates that histone proteins may be important factors in establishing infections by pathogenic bacteria in the human gastrointestinal tract.…”

Evolution of the Chaperone/Usher Assembly Pathway: Fimbrial Classification Goes Greek

“…F6 fimbriae are rigid filaments that are 7 nm in diameter (153) (86). F6 fimbriae bind to receptors found in the brush border of piglet intestinal cells (57,58,71,171), which have recently been identified as histone H1 proteins (372).…”

Major virulence factors of enterotoxigenic Escherichia coli in pigs

“…The fasG K117 residue is required only for binding to the glycolipid receptor, whereas two fragments from the amino acid residues at position 211 (glutamine) to 220 (serine) and from position 20 (aspartic acid) to 41 (serine), respectively, are required specifically for the recognition of the glycoprotein receptor (Choi and Schifferli 2001). Zhu et al (2005) indicated that the intestinal protein receptors for 987P are histone H1 proteins. The histone H1 molecules stabilize the sulfatidefimbriae interaction by simultaneously binding to the membrane and to 987P.…”