Staphylococcus aureus aconitase inactivation unexpectedly inhibits post-exponential-phase growth and enhances stationary-phase survival

Greg A. Somerville, Michael S. Chaussee, Carrie I. Morgan, J. Ross Fitzgerald, David W. Dorward, Lawrence J. Reitzer, James M. Musser

Research output: Contribution to journalArticle

112 Citations (Scopus)

Abstract

Staphylococcus aureus preferentially catabolizes glucose, generating pyruvate, which is subsequently oxidized to acetate under aerobic growth conditions. Catabolite repression of the tricarboxylic acid (TCA) cycle results in the accumulation of acetate. TCA cycle derepression coincides with exit from the exponential growth phase, the onset of acetate catabolism, and the maximal expression of secreted virulence factors. These data suggest that carbon and energy for post-exponential-phase growth and virulence factor production are derived from the catabolism of acetate mediated by the TCA cycle. To test this hypothesis, the aconitase gene was genetically inactivated in a human isolate of S. aureus, and the effects on physiology, morphology, virulence factor production, virulence for mice, and stationary-phase survival were examined. TCA cycle inactivation prevented the post-exponential growth phase catabolism of acetate, resulting in premature entry into the stationary phase. This phenotype was accompanied by a significant reduction in the production of several virulence factors and alteration in host-pathogen interaction. Unexpectedly, aconitase inactivation enhanced stationaryphase survival relative to the wild-type strain. Aconitase is an iron-sulfur cluster-containing enzyme that is highly susceptible to oxidative inactivation. We speculate that reversible loss of the iron-sulfur cluster in wild-type organisms is a survival strategy used to circumvent oxidative stress induced during host-pathogen interactions. Taken together, these data demonstrate the importance of the TCA cycle in the life cycle of this medically important pathogen.

Original languageEnglish (US)
Pages (from-to)6373-6382
Number of pages10
JournalInfection and immunity
Volume70
Issue number11
DOIs
StatePublished - Nov 1 2002

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Aconitate Hydratase
Citric Acid Cycle
Staphylococcus aureus
Virulence Factors
Acetates
Survival
Host-Pathogen Interactions
Growth
Sulfur
Iron
Catabolite Repression
Life Cycle Stages
Pyruvic Acid
Virulence
Intercellular Signaling Peptides and Proteins
Oxidative Stress
Carbon
Phenotype
Glucose
Enzymes

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

Cite this

Staphylococcus aureus aconitase inactivation unexpectedly inhibits post-exponential-phase growth and enhances stationary-phase survival. / Somerville, Greg A.; Chaussee, Michael S.; Morgan, Carrie I.; Fitzgerald, J. Ross; Dorward, David W.; Reitzer, Lawrence J.; Musser, James M.

In: Infection and immunity, Vol. 70, No. 11, 01.11.2002, p. 6373-6382.

Research output: Contribution to journalArticle

Somerville, Greg A. ; Chaussee, Michael S. ; Morgan, Carrie I. ; Fitzgerald, J. Ross ; Dorward, David W. ; Reitzer, Lawrence J. ; Musser, James M. / Staphylococcus aureus aconitase inactivation unexpectedly inhibits post-exponential-phase growth and enhances stationary-phase survival. In: Infection and immunity. 2002 ; Vol. 70, No. 11. pp. 6373-6382.
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