The receptor locus for Escherichia coli F4ab/F4ac in the pig maps distal to the MUC4–LMLN region

Abstract

Enterotoxigenic Escherichia coli (ETEC) with fimbriae of the F4 family are one of the major causes of diarrhea and death among neonatal and young piglets. Bacteria use the F4 fimbriae to adhere to specific receptors expressed on the surface of the enterocytes. F4 fimbriae exist in three different antigenic variants, F4ab, F4ac, and F4ad, of which F4ac is the most common. Resistance to ETEC F4ab/F4ac adhesion in pigs has been shown to be inherited as an autosomal recessive trait. In previous studies the ETEC F4ab/F4ac receptor locus (F4bcR) was mapped to the q41 region on pig chromosome 13. A polymorphism within an intron of the mucin 4 (MUC4) gene, which is one of the possible candidate genes located in this region, was shown earlier to cosegregate with the F4bcR alleles. Recently, we discovered a Large White boar from a Swiss experimental herd with a recombination between F4bcR and MUC4. A three-generation pedigree including 45 offspring was generated with the aim to use this recombination event to refine the localization of the F4bcR locus. All pigs were phenotyped using the microscopic adhesion test and genotyped for a total of 59 markers. The recombination event was mapped to a 220-kb region between a newly detected SNP in the leishmanolysin-like gene (LMLN g.15920) and SNP ALGA0072075. In this study the six SNPs ALGA0072075, ALGA0106330, MUC13-226, MUC13-813, DIA0000584, and MARC0006918 were in complete linkage disequilibrium with F4bcR. Based on this finding and earlier investigations, we suggest that the locus for F4bcR is located between the LMLN locus and microsatellite S0283.

Refined Candidate Region for F4ab/ac Enterotoxigenic Escherichia coli Susceptibility Situated Proximal to MUC13 in Pigs

“…The low significant P -value of the Indel MUC13 marker (Table S2; Figure 5A) confirmed our previous results that MUC13 is not the causal gene for F4ab/ac ETEC susceptibility. Four markers of the Porcine SNP60 BeadChip (ALGA0072075 [GenBank:NC_010455.4; 144832256], ALGA0106330 (SNP3), DIAS0000584 [GenBank:NC_010455.4; 145414240] and MARC0006918 [unknown position]), and 2 additional markers ( MUC13 -226 [GenBank:NC_010455.4; 145,010,437] and MUC13 -813 [GenBank:NC_010455.4; 145,016,914]) were in complete LD with the F4ab/acR locus in a Swiss experimental herd [31]. Except for one sow and some of her offspring, markers ALGA0106330 (SNP 3), MUC13 -226 and MUC13 -813 were not in LD with the F4ab/acR locus [32].…”

Animal EnterotoxigenicEscherichia coli

“…MUC4-mediated susceptibility was linked to the presence of high molecular weight glycoproteins (172). Based on linkage disequilibrium for MUC13 (173), and more specifically for six SNPs (two in MUC13) with the F4ab/ac receptor locus, this locus was located between the LMLN locus and microsatellite S0283 (174). Further studies confirmed a link between the F4ac receptor locus and MUC13, and pigs expressing at least one transcript predicted to encode a highly O-glycosylated MUC13 protein (MUC13B) were F4ac-susceptible, whereas pigs homozygous for the non-glycosylated allele (MUC13A) were F4ac resistant (175).…”

Cell membrane-anchored MUC4 promotes tumorigenicity in epithelial carcinomas

“…MUC4 associates with the host receptor of enterotoxigenic Escherichia coli [64–68]. Moreover, E. coli strains from phylogroup B2 harboring a pks+ island can produce a peptide-polyketide hybrid compound termed colibactin, which can trigger premature and transmissible senescence in mammalian cells, resulting in colon cancer [69].…”