A DNA polymorphism influencing alpha(1,2)fucosyltransferase activity of the pig FUT1 enzyme determines susceptibility of small intestinal epithelium to Escherichia coli F18 adhesion.
The alpha(1,2)fucosyltransferases (FUT1 and FUT2) contribute to the formation of blood group antigen structures, which are present on cell membranes and in secretions. In the present study we demonstrate that both FUT1 and FUT2 are expressed in the pig small intestine. FUT1 polymorphisms influence adhesion of F18 fimbriated Escherichia coli (ECF18) to intestinal mucosa, and FUT2 is associated with expression of erythrocyte antigen 0. The FUT1 polymorphisms result in amino acid substitutions at positions 103 (Ala-->Thr) and 286 (Arg-->Glu). Tightly controlled expression of the FUT2 gene results in either an abundance or an absence of mRNA in small intestinal mucosa. ECF18-resistant animals were shown to be homozygous for threonine at amino acid 103 of the FUT1 enzyme. Susceptibility to ECF18 adhesion appeared to be solely dependent on the activity of FUT1 in intestinal epithelia. In intestinal mucosae of ECF18-resistant pigs which expressed FUT1 but not FUT2 RNA, the levels of alpha(1,2)fucosyltransferase activity were significantly lower (28- to 45-fold, P<0.001) than in susceptible pigs. Moreover, lysates of CHO cells transfected with FUT1 constructs encoding threonine at amino acid position 103 also showed significantly reduced enzyme activity compared with constructs encoding alanine at this position. Our genetic and enzymatic studies support the hypothesis that the FUT1 enzyme, and particularly the amino acid at position 103, is likely important in the synthesis of a structure that enables adhesion of ECF18 bacteria to small intestinal mucosa.
Meijerink
E
E
Institute of Animal Science, Swiss Federal Institute of Technology, ETH-Zentrum, Zurich.
Neuenschwander
S
S
Fries
R
R
Dinter
A
A
Bertschinger
H U
HU
Stranzinger
G
G
Vögeli
P
P
D000818:Animals; D001422:Bacterial Adhesion / Q000502:physiology; D001483:Base Sequence; D016466:CHO Cells; D006224:Cricetinae; D018076:DNA, Complementary; D004926:Escherichia coli / Q000502:physiology*; D005647:Fucosyltransferases / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007413:Intestinal Mucosa / Q000382:microbiology; D007421:Intestine, Small / Q000382:microbiology*; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D012333:RNA, Messenger; D013552:Swine; D000097631:Galactoside 2-alpha-L-fucosyltransferase
D018076:DNA, Complementary; D005647:Fucosyltransferases; D012333:RNA, Messenger; D000097631:Galactoside 2-alpha-L-fucosyltransferase