Reactive oxygen species induce antibiotic tolerance during systemic Staphylococcus aureus infection
NATURE MICROBIOLOGY(2019)
摘要
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.
更多查看译文
关键词
Antibiotics,Bacterial host response,Infection,Life Sciences,general,Microbiology,Medical Microbiology,Parasitology,Infectious Diseases,Virology
AI 理解论文
溯源树
样例
![](https://originalfileserver.aminer.cn/sys/aminer/pubs/mrt_preview.jpeg)
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要