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Redox signaling mechanisms under infection conditions and antibiotics in the major pathogen Staphylococcus aureus

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Event details

Date and time 01.10.2019 16:3018:00  
Place and room
Speaker Prof. Haike Antelmann
Category Conferences - Seminars
Staphylococcus aureus has to cope with reactive oxygen, electrophile and chlorine species (ROS, RES, RCS) during infections and antibiotics treatment. We are interested in redox signaling and defense mechanisms of redox-active species, such as HOCl, quinones and antibiotics in S. aureus. The Rrf2- family regulator HypR was described as novel redox-sensitive repressor that controls the flavin disulfide reductase MerA and directly senses and responds to HOCl, diamide and allicin stress via a thiol-disulfide switch in S. aureus. MerA was shown to functions as disulfide reductase to protect S. aureus against HOCl and allicin stress and increased survival in J774A.1 macrophage infection assays.
In addition, the MarR-type regulator MhqR was identified as novel quinone-sensing repressor of the mhqRED operon, which is involved in quinone detoxification. The MhqR repressor is directly inactivated by quinones and likely binds to a specific quinone-binding pocket. In phenotypic assays, the mhqR deletion mutant was resistant to MHQ and quinone-like antimicrobials, such as pyocyanin, ciprofloxacin, norfloxacin and rifampicin. Moreover, the MhqR regulon contributes to an improved survival under lethal ROS and after long-term infections in S. aureus.
Apart from redox-sensing regulators, the low molecular weight thiol bacillithiol (BSH) plays an important role to maintain the thiol-redox homeostasis in S. aureus. Under HOCl stress, BSH forms mixed disulfides with proteins thiols, termed as protein S-bacillithiolation to protect redox-sensitive thiols against overoxidation and to regulate protein functions. The glycolytic glyceraldehyde-3- phosphate dehydrogenase GapDH and the aldehyde dehydrogenase AldA were discovered as most abundant targets for S-bacillithiolation in S. aureus. The reversal of S-bacillithiolation is redox- controlled by the Brx/BSH/YpdA pathway. Moreover, the bacilliredoxin BrxA and the BSSB reductase YpdA were shown to be essential under oxidative stress and infections conditions. In conclusion, our studies discovered novel redox-regulators and important thiol-switches that play essential role for survival under HOCl, quinones and infection conditions in S. aureus.

Practical information

  • General public
  • Free

Organizer

  • Prof. Yimon Aye

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Tags

cbseminar

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