Genetic manipulation of 6-phosphofructo-1-kinase and fructose 2,6-bisphosphate levels affects the extent to which benzoic acid inhibits the growth of Saccharomyces cerevisiae.
The mechanisms by which the weak acid preservative benzoic acid inhibits the growth of Saccharomyces cerevisiae have been investigated. A reduction in the pyruvate kinase level, which decreases glycolytic flux, did not increase the sensitivity of yeast to benzoic acid. However, a decrease in 6-phosphofructo-1-kinase (PF1K), which does not affect glycolytic flux, did increase sensitivity to benzoic acid. Also, resistance was increased by elevating PF1K levels. Hence, resistance to benzoic acid was not dependent upon optimum glycolytic flux, but upon an adequate PF1K activity. Benzoic acid was shown to depress fructose 2,6-bisphosphate levels in YKC14, a mutant with low PF1K levels. This effect was partially suppressed by overexpressing constitutively active 6-phosphofructo-2-kinase (Pfk26(Asp644)) or by inactivating fructose-2,6-bisphosphatase (in a Deltafbp26 mutant). The inactivation of PF2K (in a Deltapfk26 Deltapfk27 mutant) increased benzoic acid sensitivity. Therefore, the antimicrobial effects of benzoic acid can be relieved, at least in part, by the genetic manipulation of PF1K or fructose 2,6-bisphosphate levels.
Pearce
Amanda K
AK
Molecular and Cell Biology, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK1.
Booth
Ian R
IR
Molecular and Cell Biology, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK1.
Brown
Alistair J P
AJP
Molecular and Cell Biology, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK1.
D000935:Antifungal Agents / Q000494:pharmacology*; D019817:Benzoic Acid / Q000494:pharmacology*; D005635:Fructosediphosphates / Q000235:genetics / Q000378:metabolism*; D006019:Glycolysis; D010732:Phosphofructokinase-1 / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics / Q000254:growth & development
D000935:Antifungal Agents; D005635:Fructosediphosphates; C027652:fructose 2,6-diphosphate; D019817:Benzoic Acid; D010732:Phosphofructokinase-1; C068652:1-phosphofructokinase