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Reactive oxygen species induce antibiotic tolerance during systemic Staphylococcus aureus infection.

Publication ,  Journal Article
Rowe, SE; Wagner, NJ; Li, L; Beam, JE; Wilkinson, AD; Radlinski, LC; Zhang, Q; Miao, EA; Conlon, BP
Published in: Nat Microbiol
February 2020

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 sepsis1. These more serious infections usually arise from an initial bloodstream infection and are frequently recalcitrant to antibiotic treatment1. Phagocytosis by macrophages and neutrophils is the primary mechanism through which S. aureus infection is controlled by the immune system2. Macrophages have been shown to be a major reservoir of S. aureus in vivo3, 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.

Duke Scholars

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Published In

Nat Microbiol

DOI

EISSN

2058-5276

Publication Date

February 2020

Volume

5

Issue

2

Start / End Page

282 / 290

Location

England

Related Subject Headings

  • Staphylococcus aureus
  • Staphylococcal Infections
  • Respiratory Burst
  • Reactive Oxygen Species
  • Phagocytosis
  • Neutrophils
  • NADPH Oxidases
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
 

Citation

APA
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Rowe, S. E., Wagner, N. J., Li, L., Beam, J. E., Wilkinson, A. D., Radlinski, L. C., … Conlon, B. P. (2020). Reactive oxygen species induce antibiotic tolerance during systemic Staphylococcus aureus infection. Nat Microbiol, 5(2), 282–290. https://doi.org/10.1038/s41564-019-0627-y
Rowe, Sarah E., Nikki J. Wagner, Lupeng Li, Jenna E. Beam, Alec D. Wilkinson, Lauren C. Radlinski, Qing Zhang, Edward A. Miao, and Brian P. Conlon. “Reactive oxygen species induce antibiotic tolerance during systemic Staphylococcus aureus infection.Nat Microbiol 5, no. 2 (February 2020): 282–90. https://doi.org/10.1038/s41564-019-0627-y.
Rowe SE, Wagner NJ, Li L, Beam JE, Wilkinson AD, Radlinski LC, et al. Reactive oxygen species induce antibiotic tolerance during systemic Staphylococcus aureus infection. Nat Microbiol. 2020 Feb;5(2):282–90.
Rowe, Sarah E., et al. “Reactive oxygen species induce antibiotic tolerance during systemic Staphylococcus aureus infection.Nat Microbiol, vol. 5, no. 2, Feb. 2020, pp. 282–90. Pubmed, doi:10.1038/s41564-019-0627-y.
Rowe SE, Wagner NJ, Li L, Beam JE, Wilkinson AD, Radlinski LC, Zhang Q, Miao EA, Conlon BP. Reactive oxygen species induce antibiotic tolerance during systemic Staphylococcus aureus infection. Nat Microbiol. 2020 Feb;5(2):282–290.

Published In

Nat Microbiol

DOI

EISSN

2058-5276

Publication Date

February 2020

Volume

5

Issue

2

Start / End Page

282 / 290

Location

England

Related Subject Headings

  • Staphylococcus aureus
  • Staphylococcal Infections
  • Respiratory Burst
  • Reactive Oxygen Species
  • Phagocytosis
  • Neutrophils
  • NADPH Oxidases
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice