Aims: A contribution towards the elucidation of the mechanisms of tannins on bacteria growth inhibition, with particular focus on the interaction between tannins and bacterial proteins. Methods and results: The interaction between tannic acid (TA) and Lactobacillus hilgardii, a wine spoilage bacterium, was investigated by a combination of physiologic and proteomic approaches. Growing tests were performed on medium supplemented with TA at concentrations ranging from 100 to 1000 mg l(-1) demonstrating the inhibitory effect of TA on the growth rate. Total proteins extracted from cells unexposed and exposed to TA were then analysed by 2D-electrophoresis and significant quantitative variations with a marked decrease of protein intensity upon TA exposure were observed. Most of the proteins, identified by ESI tandem Mass Spectrometry, were metabolic enzymes of different pathways, located in cytoplasm and membrane. Conclusions: The effects of TA on cells are deduced by the involvement of metabolic enzymes, and functional proteins on the tannin-protein interaction. These results might be related to the altered functions of the cell metabolism. Significance and impact o the study: The possible role of tannins in the inhibition of the bacterial survival and growth in a natural environment such as wine. A similar approach could be applied for evaluating the effects of tannins on food borne and pathogenic bacteria.