Two mechanisms for growth inhibition by elevated transport of sugar phosphates in Escherichia coli.
The Escherichia coli uhp T gene encodes an active transport system for sugar phosphates. When the uhp T gene was carried on a multicopy plasmid, amplified levels of transport activity occurred, and growth of these strains was inhibited upon the addition of various sugar phosphates. Two different mechanisms for this growth inhibition were distinguished. Exposure to glucose-6-phosphate, fructose-6-phosphate or mannose-6-phosphate, which enter directly into the glycolytic pathway, resulted in cessation of growth and substantial loss of viability. Cell killing was correlated with the production of the toxic metabolite, methylglyoxal. In contrast, addition of 2-deoxyglucose-6-phosphate, galactose-6-phosphate, glucosamine-6-phosphate or arabinose-5-phosphate, which do not directly enter the glycolytic pathway, resulted in growth inhibition without engendering methylglyoxal production or cell death. Inhibition of growth could result from excessive accumulation of organophosphates in the cell or depletion of inorganic phosphate pools as a result of the sugar-P/Pi exchange process catalysed by UhpT. The phosphate-dependent uptake of glycerol-3-phosphate by the GlpT antiporter was strongly inhibited under conditions of elevated sugar-phosphate transport. There are thus two separate toxic effects of elevated sugar-phosphate transport, one of which was lethal and related to increased flux through glycolysis. It is likely that the control of uhpT transcription by catabolite repression exists to limit the level of UhpT transport activity and thereby prevent the toxic events that result from elevated uptake of its substrates.
Kadner
R J
RJ
Department of Microbiology, School of Medicine, University of Virginia, Charlottesville 22908.
Murphy
G P
GP
Stephens
C M
CM
D001426:Bacterial Proteins / Q000378:metabolism; D001692:Biological Transport; D002352:Carrier Proteins / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D003470:Culture Media / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects* / Q000254:growth & development*; D029968:Escherichia coli Proteins; D005636:Fructosephosphates / Q000494:pharmacology; D005695:Galactosephosphates / Q000494:pharmacology; D015964:Gene Expression Regulation, Bacterial; D019298:Glucose-6-Phosphate / Q000031:analogs & derivatives; D005958:Glucosephosphates / Q000494:pharmacology; D005994:Glycerophosphates / Q000378:metabolism; D006019:Glycolysis; D008360:Mannosephosphates / Q000494:pharmacology; D009004:Monosaccharide Transport Proteins; D010428:Pentosephosphates / Q000494:pharmacology; D011765:Pyruvaldehyde / Q000378:metabolism; D013403:Sugar Phosphates / Q000378:metabolism*
D001426:Bacterial Proteins; D002352:Carrier Proteins; D003470:Culture Media; D029968:Escherichia coli Proteins; D005636:Fructosephosphates; D005695:Galactosephosphates; D005958:Glucosephosphates; D005994:Glycerophosphates; D008360:Mannosephosphates; D009004:Monosaccharide Transport Proteins; D010428:Pentosephosphates; D013403:Sugar Phosphates; C063498:UhpT protein, E coli; C028055:arabinose 5-phosphate; C015785:2-deoxyglucose-6-phosphate; C027693:mannose-6-phosphate; D019298:Glucose-6-Phosphate; C038269:galactose-6-phosphate; C027618:fructose-6-phosphate; D011765:Pyruvaldehyde; C029620:alpha-glycerophosphoric acid