CONICET | Buscador de Institutos y Recursos Humanos

The impediment of Escherichia coli attachment to the urinary tract can interrupt pyelonephritis at the earliest stages of colonisation. Since P fimbriae carry adhesin proteins capable of specific binding to renal receptors, many organic compounds were assayed as P fimbriation inhibitors. Clofibric (CL) and ethacrynic (ET) acids are weak organic acids structurally related, which are administered in the treatment of hypertriglyceridemia and to enhance diuresis, respectively. Because of these agents are mainly excreted by the renal route in an unaltered form, they are potentially active in the urinary tract. This study described that a pyelonephritogenic E. coli strain, grown in the presence of sub- MICs of CL or ET (0.1 and 1 mM), exhibited markedly altered capacity of P1 erythrocytes agglutination and drastic decrease in fimbriation ?demonstrated by electron microscopy and by quantification of the superficial proteins- in in vitro assays. The protein contents in the fimbrial extracts were reduced to a 17 - 25 % referred to control cells (without compounds). In vivo assays were performed in an experimental model of ascending urinary tract infection in BALB/c mice. The treatment with therapeutic doses of the drugs, administered daily from two days before the bacterial challenge up to the end of the experiment, diminished the renal infection to undetectable values of CFUs after 7 or 10 days of exposure. Within this period CL did not produce alterations of the renal parenchyma, nor elevations of blood urea or creatinine. On the contrary, ET treatment demonstrated pyelitis and tubular cellular desquamation after 10 days of exposure. The results suggest that CL may be useful for short term prophylaxis of recurrent urinary tract infections.

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