Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0014118 (
endocarditis
)
15,629
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Staphylococcus aureus is a major human pathogen that causes an array of infections ranging from minor skin infections to more serious infections, including osteomyelitis,
endocarditis
, necrotizing pneumonia and sepsis
1
. These more serious infections usually arise from an initial bloodstream infection and are frequently recalcitrant to antibiotic treatment
1
. Phagocytosis by macrophages and neutrophils is the primary mechanism through which S. aureus infection is controlled by the immune system
2
. Macrophages have been shown to be a major reservoir of S. aureus in vivo
3
, but the role of macrophages in the induction of antibiotic tolerance has not been explored. Here, we show that macrophages not only fail to efficiently kill phagocytosed S. aureus, but also induce tolerance to multiple antibiotics. Reactive oxygen species generated by respiratory burst attack iron-sulfur cluster-containing proteins, including
TCA
-cycle enzymes, result in decreased respiration, lower ATP and increased antibiotic tolerance. We further show that respiratory burst induces antibiotic tolerance in the spleen during a murine systemic infection. These results suggest that a major component of the innate immune response is antagonistic to the bactericidal activities of antibiotics.
...
PMID:Reactive oxygen species induce antibiotic tolerance during systemic Staphylococcus aureus infection. 3204 30
