bi7b00570_si_001.pdf (291.85 kB)
Staphylococcus aureus CidC Is a Pyruvate:Menaquinone Oxidoreductase
journal contribution
posted on 2017-08-15, 00:00 authored by Xinyan Zhang, Kenneth W. Bayles, Sorin LucaRecent
studies have revealed an important role for the Staphylococcus
aureus CidC enzyme in cell death during the
stationary phase and in biofilm development and have contributed to
our understanding of the metabolic processes that are important in
the induction of bacterial programmed cell death (PCD). To gain more
insight into the characteristics of this enzyme, we performed an in-depth
biochemical and biophysical analysis of its catalytic properties. In vitro experiments show that this flavoprotein catalyzes
the oxidative decarboxylation of pyruvate to acetate and carbon dioxide.
CidC efficiently reduces menadione, but not CoenzymeQ0,
suggesting a specific role in the S. aureus respiratory
chain. CidC exists as a monomer under neutral-pH conditions but tends
to aggregate and bind to artificial lipid membranes at acidic pH,
resulting in enhanced enzymatic activity. Unlike its Escherichia
coli counterpart, PoxB, CidC does not appear to be activated
by other amphiphiles like Triton X-100 or octyl β-d-glucopyranoside. In addition, only reduced CidC is protected from
proteolytic cleavage by chymotrypsin, and unlike its homologues in
other bacteria, protease treatment does not increase CidC enzymatic
activity. Finally, CidC exhibits maximal activity at pH 5.5–5.8
and negligible activity at pH 7–8. The results of this study
are consistent with a model in which CidC functions as a pyruvate:menaquinone
oxidoreductase whose activity is induced at the cellular membrane
during cytoplasmic acidification, a process previously shown to be
important for the induction of bacterial PCD.