Imperial College London
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Dr Jessica Rowley

Faculty of Natural Sciences, Department of Life Sciences

Facility Manager
 
 
 
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Contact

 

j.rowley

 
 
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Location

 

Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Ha:2020:10.1128/mBio.02288-20,
author = {Ha, KP and Clarke, RS and Kim, G-L and Brittan, JL and Rowley, JE and Mavridou, DAI and Parker, D and Clarke, TB and Nobbs, AH and Edwards, AM},
doi = {10.1128/mBio.02288-20},
journal = {mBio},
title = {Staphylococcal DNA repair Is required for infection},
url = {http://dx.doi.org/10.1128/mBio.02288-20},
volume = {11},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - To cause infection, Staphylococcus aureus must withstand damage caused by host immune defenses. 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 being 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 reactive oxygen species (ROS) generated by the respiratory burst, which are repaired by RexAB, leading to the induction of the mutagenic SOS response. We found that RexAB homologues in Enterococcus faecalis and Streptococcus gordonii also promoted the 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 the repair of this damage by an AddAB-family enzyme enables the survival of Gram-positive pathogens during infection.IMPORTANCE To cause infection, bacteria must survive attack by the host immune system. For many bacteria, including the major human pathogen Staphylococcus aureus, the greatest threat is posed by neutrophils. These immune cells ingest the invading organisms and try to kill them with a cocktail of chemicals that includes reactive oxygen species (ROS). The ability of S. aureus to survive this attack is crucial for the progression of infection. However, it was not clear how the ROS damaged S. aureus and how the bacterium repaired this damage. In this work, we show that ROS cause breaks
AU  - Ha,KP
AU  - Clarke,RS
AU  - Kim,G-L
AU  - Brittan,JL
AU  - Rowley,JE
AU  - Mavridou,DAI
AU  - Parker,D
AU  - Clarke,TB
AU  - Nobbs,AH
AU  - Edwards,AM
DO  - 10.1128/mBio.02288-20
PY  - 2020///
SN  - 2150-7511
TI  - Staphylococcal DNA repair Is required for infection
T2  - mBio
UR  - http://dx.doi.org/10.1128/mBio.02288-20
UR  - https://www.ncbi.nlm.nih.gov/pubmed/33203752
UR  - http://hdl.handle.net/10044/1/84823
VL  - 11
ER  -
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