The Pyruvate-Tricarboxylic Acid Cycle Node

Abstract

Background: Yersinia pseudotuberculosis is a human pathogen and the ancestor of Y. pestis. Results: The pyruvate-tricarboxylic acid cycle node in the carbon core metabolism of Y. pseudotuberculosis is a focal point of its virulence control system. Conclusion: Mutants genetically perturbed at this metabolic control point are less virulent in mouse infection studies. Significance: Learning how pathogenic traits are controlled is crucial for finding novel drug targets against the pathogen.

Metabolic flux analyses of Pseudomonas aeruginosa cystic fibrosis isolates

“…These metabolic changes are associated with increases in survivability and growth within the oxidative environment of activated macrophages in Salmonella typhiurium [122,123], attenuation of virulence in Salmonella enterica and Yersinia pseudotuberculosis [76,124], and decrease in type III secretion system expression in Y.…”

“…pseudotuberculosis and P. aeruginosa [76,125,126]. Finally, the glyoxylate shunt has been implicated in pathogenesis of organisms in human disease [127].…”

“…Several recent studies have analyzed the metabolic interactions of pathologically relevant bacteria within their host environment [74,75] and metabolic differences between mutant strains [76]. A recent study of pathogenesis related metabolism in P. aeruginosa employed MFA to describe 17 uropathogenic strains [77].…”

A Precise Temperature-Responsive Bistable Switch Controlling Yersinia Virulence

“…the afimbrial adhesin PsaA as well as lipopolysaccharide synthesis genes are activated by RovA of Y . pseudotuberculosis [24]. Although beneficial for the initiation of the infection, they are likely to trigger innate immunity-mediated antimicrobial responses when expressed in deeper tissues.…”

“…In addition, several general stress adaptation genes ( ibpAB , uspA , cspB , C1-3 , D , E ) are activated by RovA, which could support survival in the lumen of the intestine and/or in the external environment. The analysis of the RovA regulon further uncovered different metabolic programs for the wild-type and a rovA mutant [24], which may endow the RovA OFF population with a better fitness within lymphatic tissues. In fact, multiple enzymes of the pyruvate-TCA cycle ( icdA , sucDCB , gltA , acnAB , aceE , F ) are down-regulated in a rovA mutant, whereas several enzymes of the amino acid and nucleotide transport and metabolism are induced [24].…”