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Background  The extensive use of antibiotics in medicine has raised serious concerns about biosafety. However, the effect of antibiotic application on the adaptive evolution of microorganisms, especially to probiotic bacteria, has not been well characterized. Thus, the objective of the current work was to investigate how antibiotic selection forces might drive genome adaptation using  Lactobacillus  ( L .)  casei  Zhang as a model.    Methods  Two antibiotics, amoxicillin and gentamicin, were consistently applied to the laboratory culture of  L. casei  Zhang. We then monitored the mutations in the bacterial genome and changes in the minimum inhibitory concentrations (MICs) of these two antibiotics along a 2000-generation-cultivation lasted over 10 months.    Results  We found an approximately 4-fold increase in the genome mutation frequency of  L. casei  Zhang, i.e. 3.5 × 10 -9  per base pair per generation under either amoxicillin or gentamicin stress, when compared with the parallel controls grown without application of any antibiotics. The increase in mutation frequency is significantly lower than that previously reported in  Escherichia  ( E .)  coli . The rate of  de novo  mutations, i.e. 20 per genome, remained low and stable throughout the long-term cultivation. Moreover, the accumulation of new mutations stopped shortly after the maximum bacterial fitness (i.e. the antibiotic MICs) was reached.    Conclusions  Our study has shown that the probiotic species,  L. casei  Zhang, has high genome stability even in the presence of long-term antibiotic stresses. However, whether this is a species-specific or universal characteristic for all probiotic bacteria remains to be explored.    Electronic supplementary material  The online version of this article (doi:10.1186/s12864-017-3710-x) contains supplementary material, which is available to authorized users.

Genome adaptive evolution of Lactobacillus casei under long-term antibiotic selection pressures