The distinct binding specificities exhibited by enterobacterial type 1 fimbriae are determined by their fimbrial shafts.
Type 1 fimbriae of enterobacteria are heteropolymeric organelles of adhesion composed of FimH, a mannose-binding lectin, and a shaft composed primarily of FimA. We compared the binding activities of recombinant clones expressing type 1 fimbriae from Escherichia coli, Klebsiella pneumoniae, and Salmonella typhimurium for gut and uroepithelial cells and for various soluble mannosylated proteins. Each fimbria was characterized by its capacity to bind particular epithelial cells and to aggregate mannoproteins. However, when each respective FimH subunit was cloned and expressed in the absence of its shaft as a fusion protein with MalE, each FimH bound a wide range of mannose-containing compounds. In addition, we found that expression of FimH on a heterologous fimbrial shaft, e.g. K. pneumoniae FimH on the E. coli fimbrial shaft or vice versa, altered the binding specificity of FimH such that it closely resembled that of the native heterologous type 1 fimbriae. Furthermore, attachment to and invasion of bladder epithelial cells, which were mediated much better by native E. coli type 1 fimbriae compared with native K. pneumoniae type 1 fimbriae, were found to be dependent on the background of the fimbrial shaft (E. coli versus K. pneumoniae) rather than the background of the FimH expressed. Thus, the distinct binding specificities of different enterobacterial type 1 fimbriae cannot be ascribed solely to the primary structure of their respective FimH subunits, but are also modulated by the fimbrial shaft on which each FimH subunit is presented, possibly through conformational constraints imposed on FimH by the fimbrial shaft. The capacity of type 1 fimbrial shafts to modulate the tissue tropism of different enterobacterial species represents a novel function for these highly organized structures.
Duncan
Matthew J
MJ
Molecular Genetics and Microbiology and Pathology, Duke University Medical Center, Durham, NC 27710, USA.
Mann
Elena L
EL
Cohen
Michael S
MS
Ofek
Itzhak
I
Sharon
Nathan
N
Abraham
Soman N
SN
D000818:Animals; D001422:Bacterial Adhesion; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000378:metabolism / Q000382:microbiology; D004926:Escherichia coli / Q000378:metabolism; D036781:Fimbriae Proteins / Q000737:chemistry / Q000378:metabolism*; D010861:Fimbriae, Bacterial / Q000737:chemistry / Q000145:classification* / Q000378:metabolism*; D041981:Gastrointestinal Tract / Q000166:cytology / Q000382:microbiology; D015870:Gene Expression; D007711:Klebsiella pneumoniae / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D011485:Protein Binding; D011994:Recombinant Proteins; D012486:Salmonella typhimurium / Q000378:metabolism; D013045:Species Specificity; D013379:Substrate Specificity; D001743:Urinary Bladder / Q000166:cytology / Q000382:microbiology
D011994:Recombinant Proteins; D036781:Fimbriae Proteins