This permits us to conclude that analyzed pilicides in mM concentration are effective inhibitors of the assembly of adhesins belonging to the Dr family, and more speculatively, of other FGL-type adhesive organelles. Structural analysis of the DraB chaperone clearly showed it to be a model of the FGL subfamily of chaperones. The data presented in this article indicate that pilicides in mM concentration effectively inhibit the adherence of Dr + bacteria to the host cells, – the crucial, initial step in bacterial pathogenesis. The inhibition effect of pilicides is concentration dependent, which is a crucial property for their use as potential anti-bacterial agents.
Using quantitative assays, we determined the amount of Dr fimbriae in the bacteria cultivated in the presence of 3.5 mM of pilicides to be reduced by 75 to 81%. In comparison to the strain grown without pilicide, the Dr + bacteria cultivated in the presence of the 3.5 mM concentration of pilicides resulted in a reduction of 75 to 87% in the adherence properties to CHO cells expressing Dr fimbrial DAF receptor protein. We evaluated the anti-bacterial activity of literature pilicides as blockers of the assembly of a model example of FGL-type adhesive structures, – the Dr fimbriae encoded by a dra gene cluster of uropathogenic Escherichia coli strains. The data published to date have shown that pilicides inhibit biogenesis of type 1 and P pili of the FGS type which are encoded by uropathogenic E. Pili/fimbriae of this type belong to two subfamilies, FGS and FGL, which differ in the details of their assembly mechanism. They impair by means of a chaperone-usher pathway conserved in the Gram-negative bacteria of adhesive structures biogenesis. Pilicides are derivatives of ring-fused 2-pyridones which block the formation of the pili/fimbriae crucial to bacterial pathogenesis. The global spread of bacterial resistance has given rise to a growing interest in new anti-bacterial agents with a new strategy of action.
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