Imperial College London
Portrait Picture

DrThomasClarke

Faculty of Medicine, Department of Infectious Disease

Senior Lecturer
 
 
 
//

Contact

 

+44 (0)20 7594 2074thomas.clarke

 
 
//

Location

 

5.40DFlowers buildingSouth Kensington Campus

//

Summary

 

Publications

Citation

BibTex format

@unpublished{Ha:2020,
author = {Ha, KP and Clarke, R and Kim, G-L and Brittan, J and Rowley, J and Mavridou, D and Parker, D and Clarke, T and Nobbs, A and Edwards, A},
publisher = {bioRxiv},
title = {Staphylococcal DNA repair is required for infection},
year = {2020}
}
Download

RIS format (EndNote, RefMan)

TY  - UNPB
AB  - To cause infection, Staphylococcus aureus must withstand damage caused by host immune defences. However, the mechanisms by which staphylococcal DNA is damaged and repaired during infection are poorly understood. Using a panel of transposon mutants, we identified the rexBA operon as important for the survival of Staphylococcus aureus in whole human blood. Mutants lacking rexB were also attenuated for virulence in murine models of both systemic and skin infections. We then demonstrated that RexAB is a member of the AddAB family of helicase/nuclease complexes responsible for initiating the repair of DNA double strand breaks. Using a fluorescent reporter system, we were able to show that neutrophils cause staphylococcal DNA double strand breaks through ROS generated by the respiratory burst, which are repaired by RexAB, leading to induction of the mutagenic SOS response. We found that RexAB homologues in Enterococcus faecalis and Streptococcus gordonii also promoted survival of these pathogens in human blood, suggesting that DNA double strand break repair is required for Gram-positive bacteria to survive in host tissues. Together, these data demonstrate that DNA is a target of host immune cells, 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.
AU  - Ha,KP
AU  - Clarke,R
AU  - Kim,G-L
AU  - Brittan,J
AU  - Rowley,J
AU  - Mavridou,D
AU  - Parker,D
AU  - Clarke,T
AU  - Nobbs,A
AU  - Edwards,A
PB  - bioRxiv
PY  - 2020///
TI  - Staphylococcal DNA repair is required for infection
ER  -
Download