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2018 ; 8
(1
): 10849
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Inactivation of TCA cycle enhances Staphylococcus aureus persister cell formation
in stationary phase
#MMPMID30022089
Wang Y
; Bojer MS
; George SE
; Wang Z
; Jensen PR
; Wolz C
; Ingmer H
Sci Rep
2018[Jul]; 8
(1
): 10849
PMID30022089
show ga
Persister cells constitute a small subpopulation of bacteria that display
remarkably high antibiotic tolerance and for pathogens such as Staphylococcus
aureus are suspected as culprits of chronic and recurrent infections. Persisters
formed during exponential growth are characterized by low ATP levels but less is
known of cells in stationary phase. By enrichment from a transposon mutant
library in S. aureus we identified mutants that in this growth phase displayed
enhanced persister cell formation. We found that inactivation of either sucA or
sucB, encoding the subunits of the ?-ketoglutarate dehydrogenase of the
tricarboxylic acid cycle (TCA cycle), increased survival to lethal concentrations
of ciprofloxacin by 10-100 fold as did inactivation of other TCA cycle genes or
atpA encoding a subunit of the F(1)F(0) ATPase. In S. aureus, TCA cycle activity
and gene expression are de-repressed in stationary phase but single cells with
low expression may be prone to form persisters. While ATP levels were not
consistently affected in high persister mutants they commonly displayed reduced
membrane potential, and persistence was enhanced by a protein motive force
inhibitor. Our results show that persister cell formation in stationary phase
does not correlate with ATP levels but is associated with low membrane potential.