alpha-Haemolysin of uropathogenic E-coli induces Ca2+ oscillations in renal epithelial cells

Pyelonephritis is one of the most common febrile diseases in children. If n ot treated appropriately, it causes irreversible renal damage and accounts for a large proportion of end stage renal failures(1). Renal scarring can o ccur in the absence of inflammatory cells, indicating that bacteria may hav e a direct signalling effect on renal cells(2). Intracellular calcium ([Ca2 +](i)) oscillations can protect cells from the cytotoxic effects of prolong ed increases in intracellular calcium(3,4). However, no pathophysiologicall y relevant protein that induces such oscillations has been identified. Here we show that infection by uropathogenic Escherichia coli induces a constan t, low-frequency oscillatory [Ca2+](i) response in target primary rat renal epithelial cells induced by the secreted RTX (repeats-in-toxin) toxin alph a-haemolysin. The response depends on calcium influx through L-type calcium channels as well as from internal stores gated by inositol triphosphate. I nternal calcium oscillations induced by alpha-haemolysin in a renal epithel ial cell line stimulated production of cytokines interleukin (IL)-6 and IL- 8. Our findings indicate a novel role for alpha-haemolysin in pyelonephriti s: as an inducer of an oscillating second messenger response in target cell s, which fine-tunes gene expression during the inflammatory response.