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TCA cycle inactivation in Staphylococcus aureus alters nitric oxide production in RAW 264.7 cells

Chandirasegaran Massilamany1, Arunakumar Gangaplara, Donald J Gardner

  • 1School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Room 202, Bldg VBS, Lincoln, NE 68583, USA.

Molecular and Cellular Biochemistry
|April 27, 2011
PubMed

Insights

Staphylococcus aureus mutants lacking a functional tricarboxylic acid (TCA) cycle delay wound healing. Altered bacterial metabolism, specifically aconitase deficiency, reduces nitric oxide production, aiding immune evasion and survival.

Area of Science:

  • Microbiology
  • Immunology
  • Metabolic pathways

Background:

  • The tricarboxylic acid (TCA) cycle is crucial for bacterial energy production and virulence.
  • Staphylococcus aureus is a common pathogen causing various infections, including skin and soft tissue infections.

Purpose of the Study:

  • To investigate the role of Staphylococcus aureus TCA cycle in host immune response and infection resolution.
  • To determine if staphylococcal metabolism influences the host's innate immune system.

Main Methods:

  • Utilized a mouse soft tissue infection model with wild-type and aconitase mutant S. aureus strains.
  • Employed an in vitro system with RAW 264.7 cells exposed to different S. aureus strains.
  • Measured nitric oxide (NO(•)) production and inducible nitric oxide synthase (iNOS) expression.
  • Assessed the expression of antigen-presentation and costimulatory molecules.

Main Results:

  • Inactivation of the TCA cycle in S. aureus delayed the resolution of cutaneous ulcers in mice.
  • Lesions showed comparable inflammatory infiltrates, indicating delayed resolution was independent of immune cell recruitment.
  • In vitro, S. aureus aconitase mutants induced significantly lower nitric oxide and iNOS levels compared to wild-type.
  • Antigen-presentation and costimulatory molecule expression remained similar between groups.

Conclusions:

  • Staphylococcal metabolism, specifically TCA cycle activity, modulates the host immune response.
  • Altered bacterial metabolism allows S. aureus to evade innate immunity, potentially enhancing survival.
  • TCA cycle mutants may be prevalent in clinical isolates due to their immune-evasive properties.

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