<b>DegS regulates the aerobic metabolism of Vibrio cholerae via the ArcAisocitrate dehydrogenase pathway for growth and intestinal colonizatio</b>
收藏资源简介：
Aerobic respiration is the key driver of <i>Vibrio cholerae</i> proliferation and infection. Our previous transcriptome results suggested that <i>degS</i> knockout 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 by <i>degS</i> knockout were associated with aerobic respiration. Further results suggested that the key products of aerobic respiration, NADH and ATP, were reduced upon <i>degS</i> deletion and were not dependent on the classical σ<sup>E</sup> pathway. 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 the <i>arcA</i> gene, 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 the <i>arcA</i> gene in the <i>ΔdegS</i> strain, while levels were partially restored with overexpression of ICDH in the <i>ΔdegS</i> strain. In a growth experiment, compared to the <i>ΔdegS</i> strain, the growth rates of <i>ΔdegSΔarcA</i> and <i>ΔdegS</i>-overexpressed <i>icdh</i> strains (<i>ΔdegS+icdh</i>) were partially restored during the logarithmic growth period. Colonization of the intestines of suckling mice showed a significant reduction in the colonizing ability of the <i>ΔdegS</i> strain, similar colonizing ability of the <i>ΔdegS::degS</i> strain and the wild-type strain, and a partial recovery of the colonizing ability of the <i>ΔdegS</i>+<i>icdh</i> strain. Overall, these findings suggest that the DegS protease regulates the expression of ICDH through ArcA, thereby affecting the NADH and ATP levels of <i>V. cholerae</i> and its growth and intestinal colonization ability.
