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 attribute. Cellular mechanisms triggered by the production of toxins in the lower urinary tract have not been completely defined. Ureteral epithelial cells (UT; A. Elgavish, Infect. Immun. 61: 3304-3312, 1993) have served as an in vitro model to explore the possibility that bacterial toxins act on UT by affecting integrin-mediated adhesive properties. The effect of treatment with lipopolysaccharides (LPS) from three strains 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 attachment to collagen but not to fibronectin. The fact that LPS-5 and LT-2 inhibited an Arg-Gly-Asp sequence-sensitive component of UT attachment to fibronectin is consistent with the possibility that these toxins acted via a mechanism involving typical fibronectin receptors. UT spreading 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 with LT-2, which inhibited spreading dramatically, abolished completely a UT cell population containing more than five to eight beta 1- or beta 4-subunit-containing integrin clusters.(ABSTRACT TRUNCATED AT 250 WORDS)
Elgavish
A
A
Department of Comparative Medicine, University of Alabama at Birmingham Medical School 35294.
Pattanaik
A
A
Lloyd
K
K
Reed
R
R
D000595:Amino Acid Sequence; D001427:Bacterial Toxins / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D003094:Collagen; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects / Q000502:physiology; D005109:Extracellular Matrix / Q000378:metabolism; D005353:Fibronectins; D006801:Humans; D016023:Integrins / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008969:Molecular Sequence Data; D013682:Teichoic Acids / Q000494:pharmacology; D014551:Urinary Tract / Q000166:cytology / Q000187:drug effects*; D014553:Urinary Tract Physiological Phenomena
D001427:Bacterial Toxins; D005353:Fibronectins; D016023:Integrins; D008070:Lipopolysaccharides; D013682:Teichoic Acids; C009900:lipoteichoic acid; D003094:Collagen