Francis D H, Grange P A, Zeman D H, Baker D R, Sun R, Erickson A K
Department of Veterinary Science, South Dakota State University, Brookings, South Dakota 57007-1396, USA.
Infect Immun. 1998 Sep;66(9):4050-5. doi: 10.1128/IAI.66.9.4050-4055.1998.
Three antigenic variants of the K88 fimbrial adhesin exist in nature, K88ab, K88ac, and K88ad. Enterotoxigenic Escherichia coli (ETEC) strains that produce these fimbriae cause life-threatening diarrhea in some but not all young pigs. The susceptibility of pigs to these organisms has been correlated with the adherence of bacteria to isolated enterocyte brush borders. Whether that correlation holds for multiple K88 variants and over a broad genetic base of pigs is unknown and was the impetus for this study. We also desired to examine the correlation of the expression of a porcine intestinal brush border mucin-type glycoprotein (IMTGP) which binds K88ab and K88ac with the susceptibility of piglets to K88(+) ETEC. Of 31 neonatal gnotobiotic pigs inoculated with K88ab+ or K88ac+ ETEC, 13 developed severe diarrhea, became dehydrated, and died or became moribund. Another pig became severely lethargic but not dehydrated. In vitro brush border adherence analysis was not possible for 10 of the severely ill pigs due to colonization by challenge strains. However, of the 17 pigs that did not become severely ill, 8 (47%) had brush borders that supported the adherence of K88ab+ and K88ac+ bacteria in vitro, suggesting a poor correlation between in vitro brush border adherence and piglet susceptibility to K88(+) ETEC. By contrast, the expression of IMTGP was highly correlated with susceptibility to K88(+) ETEC. Of the 12 pigs that produced IMTGP, 11 developed severe diarrhea. The other pig that produced IMTGP became lethargic but not severely diarrheic. Only 2 of 18 pigs that did not produce IMTGP became severely diarrheic. Colonizing bacteria were observed in histologic sections of intestines from all pigs that expressed IMTGP except for the one that did not develop severe diarrhea. However, colonizing bacteria were observed in histologic sections from only one pig that did not produce IMTGP. The bacterial concentration in the jejuna and ilea of pigs expressing IMTGP was significantly greater (P < 0.005) than that in pigs not expressing IMTGP. These observations suggest the IMTGP is a biologically relevant receptor for K88ab+ and K88ac+ E. coli or a correlate for expression for such a receptor.
K88菌毛黏附素在自然界存在三种抗原变体,即K88ab、K88ac和K88ad。产生这些菌毛的产肠毒素大肠杆菌(ETEC)菌株在部分但并非所有幼猪中会引发危及生命的腹泻。猪对这些病原体的易感性与细菌对分离出的肠上皮细胞刷状缘的黏附有关。这种相关性在多种K88变体以及广泛的猪遗传基础上是否成立尚不清楚,这也是本研究的动因。我们还希望研究一种能结合K88ab和K88ac的猪肠道刷状缘黏蛋白型糖蛋白(IMTGP)的表达与仔猪对K88(+) ETEC易感性之间的相关性。在31头接种K88ab+或K88ac+ ETEC的新生无菌猪中,13头发病严重,出现脱水,死亡或濒死。另有1头发病严重,嗜睡但未脱水。由于受攻击菌株的定植,10头重病猪无法进行体外刷状缘黏附分析。然而,在17头未重病的猪中,8头(47%)的刷状缘在体外支持K88ab+和K88ac+细菌的黏附,这表明体外刷状缘黏附与仔猪对K88(+) ETEC的易感性之间相关性较差。相比之下,IMTGP的表达与对K88(+) ETEC的易感性高度相关。在12头产生IMTGP的猪中,11头发病严重,出现腹泻。另一头产生IMTGP的猪嗜睡但腹泻不严重。在18头未产生IMTGP的猪中,只有2头发病严重,出现腹泻。除了1头未重病的猪外,在所有表达IMTGP的猪的肠道组织切片中均观察到定植细菌。然而,在未产生IMTGP的猪中,仅在1头猪的组织切片中观察到定植细菌。表达IMTGP的猪空肠和回肠中的细菌浓度显著高于(P < 0.005)未表达IMTGP的猪。这些观察结果表明,IMTGP是K88ab+和K88ac+大肠杆菌的生物学相关受体或此类受体表达的一个相关指标。