| Autor: |
Ha, Kam Pou, Clarke, Rebecca S., Brittan, Jane L., Rowley, Jessica E., Mavridou, Despoina A. I., Clarke, Thomas B., Nobbs, Angela H., Edwards, Andrew M. |
| Jazyk: |
angličtina |
| Rok vydání: |
2020 |
| DOI: |
10.1101/2020.02.23.961458 |
| Popis: |
Staphylococcus aureus is a leading cause of chronic and recurrent infections of the skin, bones, joints and bloodstream. During infection, S. aureus faces the twin threats of the host immune system and therapeutic antibiotics. Since both host immune cells and antibiotics generate reactive oxygen species, we hypothesised that S. aureus may employ a common mechanism to repair damage caused by either threat. We found that staphylococcal DNA is damaged during exposure to both human neutrophils and most bactericidal antibiotics. To understand the nature of this damage and how S. aureus repairs it, we screened a panel of transposon mutants defective for various DNA repair processes. This revealed that loss of the rexBA operon significantly reduced staphylococcal survival in human blood, during incubation with purified neutrophils, in the peritoneal cavity of mice and during exposure to a large panel of bactericidal antibiotics. We then used biochemical assays to demonstrate that RexAB is a member of the AddAB family of ATP-dependent helicase/nucleases that are required for the repair of DNA double strand breaks. Finally, we found that RexAB homologues in Enterococcus faecalis and Streptococcus gordonii also promoted survival of these pathogens in human blood, suggesting that DNA repair constitutes a broadly conserved defence against neutrophils. Together, these data demonstrate that DNA is a target of host immune cells and several antibiotics, leading to double-strand breaks, and that repair of this damage by an AddAB-family enzyme enables the survival of Gram-positive pathogens during infection. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
