Bacterial thioredoxin and thioredoxin reductase as mediators for epigallocatechin 3-gallate-induced antimicrobial action

FEBS J. 2016 Feb;283(3):446-58. doi: 10.1111/febs.13587. Epub 2015 Nov 26.


Epigallocatechin 3-gallate (EGCG) is the most abundant catechin in green tea and may combat bacteria with few side-effects. Its selectivity for different bacterial infections remains unclear, and hence the identification of the underlying mechanism is of practical importance. Both the thioredoxin (Trx) system and the glutathione/glutaredoxin (Grx) system support bacterial growth. Some pathogenic bacteria are naturally deficient in the Grx system. We analyzed the effect of green tea extract (GTE) and EGCG on wild-type and null mutants of Escherichia coli with either Trx or Grx system deficiency and found that GTE and EGCG selected the Trx system as a target and killed the mutant that is exclusively dependent on Trx/Trx reductase (TrxR). EGCG inhibited the activity of both Trx1 and TrxR of E. coli in a dose-dependent and time-dependent manner. The IC50 values of EGCG for the reduced forms of E. coli Trx1/TrxR were ~ 3-4-fold lower than those for their non-reduced forms. The IC50 value of EGCG for the E. coli Trx1 system was 56-fold lower than that for the mammalian Trx1 system. The inhibition by EGCG of both Trx1 and TrxR of E. coli was irreversible. EGCG-induced inactivation of E. coli Trx1 was a second-order process, and that of E. coli TrxR was an affinity-labeling process. The covalent binding sites for EGCG in E. coli Trx1 were Trp(28) , Trp(31) and Cys(32) , and in E. coli TrxR were Cys(135) and Cys(138) . Moreover, the sensitivity of Staphylococcus aureus to EGCG was similar to that of an E. coli mutant with Grx system deficiency. EGCG-induced inactivation of Trx/TrxR in S. aureus coincided with suppressed growth of this virulent pathogen. Our findings suggest a role for EGCG-dependent Trx/TrxR inactivation in potentiating antibacterial activity of EGCG.

Keywords: antibiotics; epigallocatechin 3-gallate; glutaredoxin; green tea; thioredoxin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Catechin / analogs & derivatives*
  • Catechin / chemistry
  • Catechin / pharmacology
  • Dose-Response Relationship, Drug
  • Escherichia coli / drug effects
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Microbial Sensitivity Tests
  • Mutation
  • Staphylococcus aureus / drug effects
  • Staphylococcus aureus / growth & development
  • Structure-Activity Relationship
  • Thioredoxin-Disulfide Reductase / antagonists & inhibitors*
  • Thioredoxin-Disulfide Reductase / metabolism*
  • Thioredoxins / antagonists & inhibitors*
  • Thioredoxins / metabolism*
  • Time Factors


  • Anti-Bacterial Agents
  • Thioredoxins
  • Catechin
  • epigallocatechin gallate
  • Thioredoxin-Disulfide Reductase