INTEGRIN-MEDIATED ADHESIVE PROPERTIES OF UROEPITHELIAL CELLS ARE INHIBITED BY TREATMENT WITH BACTERIAL TOXINS

Gram-negative bacteria are a dominant cause of urinary tract infection , and their ability to produce toxins is an important virulence attrib ute. Cellular mechanisms triggered by the production of toxins in the lower urinary tract have not been completely defined. Ureteral epithel ial cells (UT; A. Elgavish, Infect. Immun. 61: 3304-3312, 1993) have s erved as an in vitro model to explore the possibility that bacterial t oxins act on UT by affecting integrin-mediated adhesive properties. Th e effect of treatment with lipopolysaccharides (LPS) from three strain s of the gram-negative Escherichia coli [055:B5 (LPS-1), 0111:B4 (LPS- 4), and 0127:B8 (LPS-5)] and lipoteichoic acids from two gram-positive bacteria, Streptococcus faecalis (LT-2) and Bacillus subtilis (LT-3), were examined. LPS-5 inhibited markedly UT attachment to collagen and fibronectin. LPS-4 had no effect, whereas LPS-1 inhibited UT attachme nt to collagen but not to fibronectin. The fact that LPS-5 and LT-2 in hibited an Arg-Gly-Asp sequence-sensitive component of UT attachment t o fibronectin is consistent with the possibility that these toxins act ed via a mechanism involving typical fibronectin receptors. UT spreadi ng was inhibited markedly by LPS-1, LT-2, and LT-3, whereas LPS-4 and LPS-5 had no effect. Because clustering of integrins is a crucial step in integrin-mediated signal transduction, the possibility that toxins inhibited spreading by affecting clustering was tested. Treatment wit h LT-2, which inhibited spreading dramatically, abolished completely a UT cell population containing more than five to eight beta(1)- or bet a(4)-subunit-containing integrin clusters. Moreover, the cell populati on displaying low numbers of beta(1)-clusters per cell decreased consi derably. LPS-5, which had no effect on spreading, did not affect clust ering of beta(1)- or beta(4)-subunit-containing integrins. Taken toget her, the present studies are consistent with the possibility that trea tment with certain bacterial toxins inhibits UT attachment and spreadi ng on collagen and fibronectin and that integrins are involved in thei r mechanism of action.