DegS regulates the aerobic metabolism ofvia the ArcA-isocitrate dehydrogenase pathway for growth and intestinal colonization.

Abstract

Aerobic respiration is the key driver ofproliferation and infection. Our previous transcriptome results suggested thatknockout downregulates a few genes involved in NADH and ATP synthesis in the aerobic respiratory pathway. In this study, non-targeted metabolomics results showed that the differential metabolites affected byknockout were associated with aerobic respiration. Further results suggested that the key products of aerobic respiration, NADH and ATP, were reduced upondeletion and were not dependent on the classical σpathway. The two-component system response factor aerobic respiration control A (ArcA) is involved in regulating NADH and ATP levels. qRT-PCR demonstrated that DegS negatively regulates the transcription of thegene, which negatively regulates the expression of isocitrate dehydrogenase (ICDH), a key rate-limiting enzyme of the tricarboxylic acid cycle. NADH and ATP levels were partially restored with the knockout of thegene in thestrain, while levels were partially restored with overexpression of ICDH in thestrain. In a growth experiment, compared to thestrain, the growth rates ofand-overexpressedstrains () were partially restored during the logarithmic growth period. Colonization of the intestines of suckling mice showed a significant reduction in the colonizing ability of thestrain, similar colonizing ability of thestrain and the wild-type strain, and a partial recovery of the colonizing ability of the+strain. Overall, these findings suggest that the DegS protease regulates the expression of ICDH through ArcA, thereby affecting the NADH and ATP levels ofand its growth and intestinal colonization ability.