EFFECT OF ACUTE YERSINIA-ENTEROCOLITICA INFECTION ON INTESTINAL BARRIER FUNCTION IN THE MOUSE

Background: Yersinia enterocolitica is an important cause of diarrhea, but little is known about the underlying mechanisms. We therefore stu died the impact of acute Y. enterocolitica infection on intestinal bar rier function in a mouse model. Methods: For this purpose CD-1 mice we re infected with Y. enterocolitica (serotype 08; 6 x 10(7) viable bact eria), and alternating current impedance analysis was performed on day s 1, 2, 3, 5, and 8 after infection. Results: The infection resulted i n a decrease in epithelial resistance from 18.0 +/- 0.9 Ohm.cm(2) (con trols) to 12.1 +/- 0.5 Ohm.cm(2) (day 1,p < 0.001), from which the ani mals recovered by day 5. To locate this loss in barrier function, the horizontal distribution of local conductances was measured by voltage scanning, yielding two results. First, conductance was homogeneously d istributed across the chamber area, excluding erosions or ulcers among the gross surface area and favoring tight junction opening as the sou rce of barrier dysfunction. Second, the conductance of villus tips was compared with that of the intervillus region (consisting of lateral v illus walls plus crypts). On day 1 the former was increased by 74% and the latter by 18%. Then, two other mechanisms of diarrhea were tested , namely malabsorption and secretion. First, the increase in Ise after the addition of 3-O-methylglucose, representing Na+-glucose cotranspo rt, was shown not to be impaired. Second, bumetanide-inhibitable I-SC, representing electrogenic Cl- secretion, also did not differ between controls and infected animals. Conclusions: Our data show that epithel ial barrier dysfunction plays a role in Y. enterocolitica infection, w hile Na+-glucose cotransport and electrogenic Cl- secretion are unalte red.