Bifunctional alcohol/aldehyde dehydrogenase AdhE controls phospho-transferase system sugar utilization and virulence gene expression by interacting PtsH in Edwardsiella piscicida.

The bifunctional alcohol/aldehyde dehydrogenase (AdhE), one of the key enzymes in the bacterial ethanol anaerobic fermentation pathway, is critical for appropriate expression of the genes for the utilization of carbon sources. Knowledge about its global roles in modulating gene expression and metabolomics remains limited. Edwardsiella bacteria includes several important zoonotic pathogenic species including Edwardsiella piscicida, a leading fish pathogen that causes severe economic losses in the aquaculture industry. It is well known to utilize few sugars. In this study, we showed that AdhE is involved in various processes including sugar utilization, bacteria growth, intracellular pH homeostasis, type III/VI secretion system (T3/T6SS) production, and survival in fish. Moreover, our unbiased metabolomics approaches revealed that AdhE modulates a large quantity of metabolic pathways, including amino acids, tricarboxylic acid (TCA) intermediates, sugar and fatty acids. Pull-down and Co-immunoprecipitation (IP) analysis revealed that AdhE interacts with the phospho-transferase system component PtsH that supports the transform of its PTS sugars including mannose to mannose-6P, the established metabolic ligand modulating EvrA activity to control T3/T6SS expression. Collectively, AdhE appears to play important roles in bacterial adapting to the internal environment changes by regulating sugar metabolic pathways and bacterial virulence expression. These observations support a model in which AdhE acts a macromolecule hub accommodating proteins to modulate the PTS and other signaling cascades related to pathogenesis and environmental adaptation in bacterial pathogens, which may provide new perspectives for attempts to attenuate bacterial virulence.