TY - JOUR
T1 - TCA cycle inactivation in Staphylococcus aureus alters nitric oxide production in RAW 264.7 cells
AU - Massilamany, Chandirasegaran
AU - Gangaplara, Arunakumar
AU - Gardner, Donald J.
AU - Musser, James M.
AU - Steffen, David
AU - Somerville, Greg A.
AU - Reddy, Jay
N1 - Funding Information:
Acknowledgments This manuscript is a contribution of the University of Nebraska Agricultural Research Division, supported in part by funds provided through the Hatch Act and by the COBRE Program from the National Center for Research Resources (P20-RR-17675, NIH), Redox Biology Center, University of Nebraska–Lincoln. Additional funding was provided by the National Institutes of Health to GAS (AI087668) and by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health.
PY - 2011/9
Y1 - 2011/9
N2 - Inactivation of the Staphylococcus aureus tricarboxylic acid (TCA) cycle delays the resolution of cutaneous ulcers in a mouse soft tissue infection model. In this study, it was observed that cutaneous lesions in mice infected with wild-type or isogenic aconitase mutant S. aureus strains contained comparable inflammatory infiltrates, suggesting the delayed resolution was independent of the recruitment of immune cells. These observations led us to hypothesize that staphylococcal metabolism can modulate the host immune response. Using an in vitro model system involving RAW 264.7 cells, the authors observed that cells cultured with S. aureus aconitase mutant strains produced significantly lower amounts of nitric oxide (NO •) and an inducible nitric oxide synthase as compared to those cells exposed to wild-type bacteria. Despite the decrease in NO • synthesis, the expression of antigen-presentation and costimulatory molecules was similar in cells cultured with wild-type and those cultured with aconitase mutant bacteria. The data suggest that staphylococci can evade innate immune responses and potentially enhance their ability to survive in infected hosts by altering their metabolism. This may also explain the occurrence of TCA cycle mutants in clinical S. aureus isolates.
AB - Inactivation of the Staphylococcus aureus tricarboxylic acid (TCA) cycle delays the resolution of cutaneous ulcers in a mouse soft tissue infection model. In this study, it was observed that cutaneous lesions in mice infected with wild-type or isogenic aconitase mutant S. aureus strains contained comparable inflammatory infiltrates, suggesting the delayed resolution was independent of the recruitment of immune cells. These observations led us to hypothesize that staphylococcal metabolism can modulate the host immune response. Using an in vitro model system involving RAW 264.7 cells, the authors observed that cells cultured with S. aureus aconitase mutant strains produced significantly lower amounts of nitric oxide (NO •) and an inducible nitric oxide synthase as compared to those cells exposed to wild-type bacteria. Despite the decrease in NO • synthesis, the expression of antigen-presentation and costimulatory molecules was similar in cells cultured with wild-type and those cultured with aconitase mutant bacteria. The data suggest that staphylococci can evade innate immune responses and potentially enhance their ability to survive in infected hosts by altering their metabolism. This may also explain the occurrence of TCA cycle mutants in clinical S. aureus isolates.
KW - Aconitase
KW - Immune evasion
KW - Nitric oxide
KW - RAW 264.7 cells
KW - Staphylococcus aureus
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U2 - 10.1007/s11010-011-0840-3
DO - 10.1007/s11010-011-0840-3
M3 - Article
C2 - 21519920
AN - SCOPUS:80051549719
SN - 0300-8177
VL - 355
SP - 75
EP - 82
JO - Molecular and Cellular Biochemistry
JF - Molecular and Cellular Biochemistry
IS - 1-2
ER -