Infection and Immunity
Infection and Immunity
5 years ago

Autoregulation and virulence control by the toxin-antitoxin system SavRS inStaphylococcus aureus.

Banghui Liu, Lu Xue, Wen Wen, Liwen Niu, Baolin Sun, Zhongliang Zhu
Toxin-antitoxin (TA) systems play diverse physiological roles such as plasmid maintenance, growth control, and persister cell formation, but their involvement in bacterial pathogenicity remains largely unknown. Here we have identified a novel type II toxin-antitoxin system SavRS and revealed the molecular mechanisms of its autoregulation and virulence control inStaphylococcus aureus.Electrophoretic mobility shift assay and isothermal titration calorimetry data indicated that the antitoxin SavR acted as the primary repressor bound to its own promoter, while the toxin SavS formed a complex with SavR to enhance the binding ability to the operator site. DNase I footprinting assay identified the SavRS-binding site containing a short and long palindrome in the promoter region. Further, mutation and DNase I footprinting assay demonstrated that the two palindromes were crucial for DNA binding and transcriptional repression. More interestingly, genetic deletion of thesavRSsystem led to the increased hemolytic activity and pathogenicity in a mouse subcutaneous abscess model. We further identified two virulence geneshlaandefbby real-time quantitative reverse transcription-PCR and demonstrated that SavR and SavRS could directly bind to their promoter regions to repress the virulence gene expression.

Publisher URL: http://doi.org/10.1128/IAI.00032-18

DOI: 10.1128/IAI.00032-18

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