The study was conducted on a model of Lactiplantibacillus plantarum, one of the most studied species widely used in the food industry as a probiotic microorganism and/or microbial starter culture. As a result of step-by-step selection from the L. plantarum 8p-a3 strain isolated from the «Lactobacterin» probiotic, the L. plantarum 8p-a3-Clr-Amx strain was obtained, showing increased resistance, compared with the parent strain, to amoxicillin-clavulanic acid (MIC 20 mcg/ml) and clarithromycin (MIC 10 mcg/ml). The L. plantarum strain DMC-S1 was isolated from the intestine of Drosophila melanogaster Canton-S line. Extracellular vesicles of this bacterium can play a significant role in the drug-resistance development and host-microbe interactions.