Polyphosphate kinase protects Salmonella enterica from weak organic acid stress.
Mutants of Salmonella enterica lacking polyphosphate kinase (ppk) grow poorly in the presence of the weak organic acids acetate, propionate, and benzoate. This sensitivity is corrected by methionine and seems to result from destabilization of MetA (homoserine transsuccinylase), the first enzyme in methionine biosynthesis. The MetA protein is known to be sensitive to thermal inactivation, and ppk mutants are more sensitive to heat-induced methionine auxotrophy. Peroxide increases the sensitivity of ppk mutants to both heat and acid and may oxidatively damage (carbonylate) destabilized MetA. While acid appears to impair methionine biosynthesis, it leads to derepression of MetA and may inhibit growth by causing toxic accumulation of denatured protein. This is supported by the observation that the overexpression of MetA in ppk mutants causes acid sensitivity that is not corrected by methionine. We propose that polyphosphate acts as a chemical chaperone that helps refold MetA and/or may stimulate proteolysis of toxic denatured protein. The instability of MetA protein may provide a metabolic fuse that blocks growth under conditions that denature proteins; the sensitivity of this fuse is modulated by polyphosphate.
Price-Carter
Marian
M
Department of Biology, University of Utah, Salt Lake City, Utah 84112, USA.
Fazzio
Thomas G
TG
Vallbona
Ester Ibañez
EI
Roth
John R
JR
D000143:Acids / Q000494:pharmacology; D000217:Acyltransferases / Q000235:genetics / Q000378:metabolism; D000222:Adaptation, Physiological; D001426:Bacterial Proteins / Q000378:metabolism; D003001:Cloning, Molecular; D004795:Enzyme Stability; D017353:Gene Deletion; D051082:Homoserine O-Succinyltransferase; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008715:Methionine / Q000096:biosynthesis / Q000378:metabolism; D016254:Mutagenesis, Insertional; D017856:Phosphotransferases (Phosphate Group Acceptor) / Q000235:genetics / Q000378:metabolism*; D011122:Polyphosphates; D011489:Protein Denaturation; D019779:Salmonella enterica / Q000201:enzymology* / Q000254:growth & development / Q000502:physiology; D012808:Sigma Factor / Q000378:metabolism
D000143:Acids; D001426:Bacterial Proteins; D011122:Polyphosphates; D012808:Sigma Factor; C069567:sigma factor KatF protein, Bacteria; D008715:Methionine; D006861:Hydrogen Peroxide; D000217:Acyltransferases; D051082:Homoserine O-Succinyltransferase; D017856:Phosphotransferases (Phosphate Group Acceptor); C022424:polyphosphate kinase