Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0393754 (
HSA
)
2,996
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The prevalence of methicillin-resitant Staphylococcus aureus (MRSA) in hospitals and the community poses an increasing health burden, which requires the discovery of alternative antimicrobials.
Allicin
(diallyl thiosulfinate) from garlic exhibits broad-spectrum antimicrobial activity against many multidrug resistant bacteria. The thiol-reactive mode of action of allicin involves its S-thioallylations of low molecular weight (LMW) thiols and protein thiols. To investigate the mode of action and stress response caused by allicin in S. aureus, we analyzed the transcriptome signature, the targets for S-thioallylation in the proteome and the changes in the bacillithiol (
BSH
) redox potential (E
BSH
) under allicin stress.
Allicin
caused a strong thiol-specific oxidative and sulfur stress response and protein damage as revealed by the induction of the PerR, HypR, QsrR, MhqR, CstR, CtsR, HrcA and CymR regulons in the RNA-seq transcriptome.
Allicin
also interfered with metal and cell wall homeostasis and caused induction of the Zur, CsoR and GraRS regulons. Brx-roGFP2 biosensor measurements revealed a strongly increased E
BSH
under allicin stress. In the proteome, 57 proteins were identified with S-thioallylations under allicin treatment, including translation factors (EF-Tu, EF-Ts), metabolic and redox enzymes (AldA, GuaB, Tpx, KatA, BrxA, MsrB) as well as redox-sensitive MarR/SarA-family regulators (MgrA, SarA, SarH1, SarS). Phenotype and biochemical analyses revealed that
BSH
and the HypR-controlled disulfide reductase MerA are involved in allicin detoxification in S. aureus. The reversal of protein S-thioallylation was catalyzed by the Brx/
BSH
/YpdA pathway. Finally, the BSSB reductase YpdA was shown to use S-allylmercaptobacillithiol (BSSA) as substrate to regenerate
BSH
in S. aureus. In conclusion, allicin results in an oxidative shift of E
BSH
and protein S-thioallylation, which can be reversed by YpdA and the Brx/
BSH
/YpdA electron pathways in S. aureus to regenerate thiol homeostasis.
...
PMID:Staphylococcus aureus responds to allicin by global S-thioallylation - Role of the Brx/BSH/YpdA pathway and the disulfide reductase MerA to overcome allicin stress. 3112 Dec 22
