Global transcriptional regulation by the CodY gene: identification of critical compounds that enhance oxidative stress resistance in Lactobacillus delbrueckii subsp. Bulgaricus.

2025-11-24
BMC microbiology 25(1)

PubMed: 41286623
DOI: 10.1186/s12866-025-04478-3

Study Design

Population: Lactobacillus delbrueckii subsp. bulgaricus in co-culture with a Streptococcus thermophilus codY gene deletion mutant strain
Methods: Utilized a S. thermophilus codY gene deletion mutant strain to explore metabolites affecting oxidative-stress resistance; the ST-1ΔcodY mutant strain was constructed by the knockout technique; metabolites were comprehensively analyzed under three different culture conditions

Background

CodY (Control of dppY) is a global transcriptional regulator of Streptococcus thermophilus (ST). In this study, we utilized a S. thermophilus codY gene deletion mutant strain to explore metabolites that may affect the oxidative-stress resistance of Lactobacillus delbrueckii subsp. bulgaricus. The context of this research is to understand the role of CodY in the interaction between S. thermophilus and L. delbrueckii, particularly focusing on the impact of CodY on the oxidative-stress resistance of L. delbrueckii.

Results

Firstly, the ST-1ΔcodY mutant strain was constructed by the knockout technique. We found that codY gene deletion significantly reduced the growth rate and resistance to oxidative stress of L. delbrueckii in co-culture, with a decrease in viable bacterial count to 5.26 ± 0.04 log(cfu/mL), and a decrease in survival by 15% and 25% under 5 mM and 10 mM H₂O₂ stress, respectively. Metabolites were comprehensively analyzed under three different culture conditions, and we identified 35 differentiated metabolites associated with CodY regulation. These metabolites were screened by their significant differential metabolite expression folds (up- or down-regulation) under different culture conditions, and Variable Importance in Projection (VIP) values assessed their significance, fold changes, and P values. Further, we identified six compounds, including lysine, 4-hydroxyphenylacetic acid, cycloleucine, glycine-L-lysine, 3-hydroxyphenylacetic acid, and N₆-acetyl-L-lysine, which significantly enhanced the oxidative-stress resistance of L. delbrueckii. The viable counts of L. delbrueckii were increased by 7.73%, 6.49%, 4.27%, 3.62%, 2.12%, and 1.38%, respectively, in the medium supplemented with these substances under the stress of 10 mM H₂O₂.

Conclusions

The study results are important for understanding the synergistic effect of the two bacteria during fermentation and their response to environmental stresses. The findings provide insights into the role of CodY in modulating the oxidative-stress resistance of L. delbrueckii and highlight the potential of identified metabolites to enhance the performance of this bacterium under stress conditions. This could have implications for the development of strategies to improve the robustness of industrial fermentation processes involving these bacteria.

Research Insights

Supplement	Dose	Health Outcome	Effect Type	Effect Size	Source
Streptococcus thermophilus ST-21	—	Improved Oxidative Stress Resistance	Beneficial	Small	View source We found that codY gene deletion significantly reduced the growth rate and resistance to oxidative stress of L. delbrueckii in co-culture... Further, we identified six compounds... which significantly enhanced the oxidative-stress resistance of L. delbrueckii.