Whole-genome sequencing and genomic-based acid tolerance mechanisms of Lactobacillus delbrueckii subsp. bulgaricus LJJ.

The probiotic efficacy and fermentative ability of Lactobacillus delbrueckii subsp. bulgaricus (L. bulgaricus), a widely used probiotic, is majorly affected by its acid tolerance. Here, we conducted whole-genome sequencing of the high acid-tolerant L. bulgaricus LJJ stored in the laboratory. Compared with the whole genome of low acid-tolerant strain L. bulgaricus ATCC11842, the results show that 16 candidate acid-tolerant genes may be involved in the regulation of the acid tolerance of L. bulgaricus LJJ. Association analysis of candidate acid-tolerant genes and acid-tolerant traits of different L. bulgaricus strains revealed that the three genes dapA, dapH, and lysC are the main reasons for the strong acid tolerance of L. bulgaricus LJJ. The results of real-time quantitative PCR (RT-qPCR) supported this conclusion. KEGG pathway analysis showed that these three acid-tolerant genes are involved in the synthesis of lysine; the synthesis of lysine may confer L. bulgaricus LJJ strong acid tolerance. This study successfully revealed the acid tolerance mechanism of L. bulgaricus LJJ and provides a theoretical basis for the subsequent selection of strains with high acid tolerance for improved probiotic functions. KEY POINTS: • Three genes are identified as acid-tolerant genes, respectively, lysC, dapA, and dapH. • LysC and dapA are the major key genes in the synthesis of lysine. • The synthesis of lysine may confer L. bulgaricus LJJ strong acid tolerance.