AimsTo investigate cell determinants of resistance to gastric acidity in Lactobacillus plantarum using comparative proteomics. Methods and ResultsAmong ten Lact.plantarum strains that were tested for their acid resistance in vitro, three strains with different phenotypes were selected for comparative proteomic analysis: LC804 (resistant), CIPA159 (intermediate) and CECT4185 (sensitive). Constitutive differences between whole-cell proteomes of the three strains were studied. Among the differentially expressed proteins between strains, 17 have previously been reported to be involved in acid resistance processes. The effect of a low-pH exposure on these proteomic patterns was investigated, which led to the identification of five putative determinants of acid resistance (heat-shock protein GrpE, methionine synthase and 30S ribosomal protein S2) or sensitivity (phosphotransacetylase and adenylosuccinate synthase). Analysis also revealed three additional proteins involved in cell envelope biogenesis (3-oxoacyl-synthase II, dTDP-glucose 4,6-dehydratase and dTDP-4-dehydrorhamnose 3,5-epimerase) likely to be key factors of intrinsic acid tolerance in Lact.plantarum. ConclusionsThe approach used in this study enabled the identification of potential markers of acid tolerance in Lact.plantarum, which may serve for phenotyping and screening purposes. Significance and Impact of the StudyThe present work represents a further step towards the identification of bacterial biomarkers for each particular probiotic feature.