title: Intermediary metabolism, Na+, the low calcium-response, and acute disease.
abstract: The variables carriage of pCD, CO2 tension, exogenous ATP, L-glutamate, Mg2+, Na+, pH, source of energy, and temperature are known to modulate the low calcium response of Yersinia pestis in vitro. The role of these effectors and the basis of their interactions are defined here with emphasis on known Y. pestis-specific missense mutations in glucose 6-phosphate dehydrogenase and aspartase, which preclude use of the hexose monophosphate pathway and prevent efficient catabolism of L-glutamic acid, respectively. A physiological Ca2+-deficient rescue scenario is provided that permits essentially full-scale growth of virulent Y. pestis (<0.1 mM Na+ and 25 mM L-glutamate at pH 6.5) with expression of pCD-encoded virulence effectors and their attendant type III secretion system. Multiplication in this environment indicates that Ca2+ prevents innate toxicity of Na+. However, Na+ actually promotes growth in Ca2+-deficient medium at pH 9.0 due to the evident action of Na+-translocating NADH-ubiquinone oxidoreductase. Another Ca2+-deficient rescue scenario (100 mM Na+ and 25 mM L-glutamate at pH 5.5) permitted growth while downregulating pCD-encoded functions. A consequence of the abrupt Na+-mediated bacteriostasis typical of aspartase-deficient Y. pestis is conversion of L-glutamate to L-aspartate with release of the latter into culture supernatant fluids. Occurrence of this event in vivo would radically alter the equilibrium of host amino acid pools thereby contributing to enhanced lethality.
authors.affiliation: Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, USA. brubake3@msu.edu
authors.forename: Robert R
authors.initials: RR
authors.lastname: Brubaker
mesh_terms: D000208:Acute Disease; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D001431:Bacteriological Techniques; D002118:Calcium / Q000378:metabolism*; D016895:Culture Media, Serum-Free; D005798:Genes, Bacterial; D006801:Humans; D020125:Mutation, Missense; D010930:Plague / Q000382:microbiology*; D012964:Sodium / Q000378:metabolism*; D014774:Virulence / Q000235:genetics / Q000502:physiology; D015010:Yersinia pestis / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D015011:Yersinia pseudotuberculosis / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity; D015012:Yersinia pseudotuberculosis Infections / Q000382:microbiology
chemical_list: D016895:Culture Media, Serum-Free; D001224:Aspartic Acid; D012964:Sodium; D002118:Calcium