Dataset Information

Allicin Induces Thiol Stress in Bacteria through S-Allylmercapto Modification of Protein Cysteines.

ABSTRACT: Allicin (diallyl thiosulfinate) from garlic is a highly potent natural antimicrobial substance. It inhibits growth of a variety of microorganisms, among them antibiotic-resistant strains. However, the precise mode of action of allicin is unknown. Here, we show that growth inhibition of Escherichia coli during allicin exposure coincides with a depletion of the glutathione pool and S-allylmercapto modification of proteins, resulting in overall decreased total sulfhydryl levels. This is accompanied by the induction of the oxidative and heat stress response. We identified and quantified the allicin-induced modification S-allylmercaptocysteine for a set of cytoplasmic proteins by using a combination of label-free mass spectrometry and differential isotope-coded affinity tag labeling of reduced and oxidized thiol residues. Activity of isocitrate lyase AceA, an S-allylmercapto-modified candidate protein, is largely inhibited by allicin treatment in vivo Allicin-induced protein modifications trigger protein aggregation, which largely stabilizes RpoH and thereby induces the heat stress response. At sublethal concentrations, the heat stress response is crucial to overcome allicin stress. Our results indicate that the mode of action of allicin is a combination of a decrease of glutathione levels, unfolding stress, and inactivation of crucial metabolic enzymes through S-allylmercapto modification of cysteines.

SUBMITTER: Muller A

PROVIDER: S-EPMC4882420 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Allicin Induces Thiol Stress in Bacteria through S-Allylmercapto Modification of Protein Cysteines.

Müller Alexandra A Eller Jakob J Albrecht Frank F Prochnow Pascal P Kuhlmann Katja K Bandow Julia Elisabeth JE Slusarenko Alan John AJ Leichert Lars Ingo Ole LI

The Journal of biological chemistry 20160323 22

Allicin (diallyl thiosulfinate) from garlic is a highly potent natural antimicrobial substance. It inhibits growth of a variety of microorganisms, among them antibiotic-resistant strains. However, the precise mode of action of allicin is unknown. Here, we show that growth inhibition of Escherichia coli during allicin exposure coincides with a depletion of the glutathione pool and S-allylmercapto modification of proteins, resulting in overall decreased total sulfhydryl levels. This is accompanied ...[more]

PMID: 27008862

Similar Datasets

Project description:Many proteins, especially those used as therapeutics, are unstable to storage and shipping temperatures, leading to increased costs in research and industry. Therefore, the design and synthesis of novel stabilizers is an important area of investigation. Herein we report new degradable polymers that stabilize proteins to environmental stressors such as refrigeration and elevated temperature. Specifically, polycaprolactones with different pendant groups were synthesized and surveyed for their ability to stabilize an important therapeutic protein to storage and shipping conditions. Ring-opening polymerization (ROP) of an allyl-substituted caprolactone monomer was carried out using the organocatalyst 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) to yield a well-defined, alkene-substituted degradable polymer, which was used as a common backbone to control for the degree of polymerization. Relevant side chains such as trehalose, lactose, glucose, carboxybetaine, and oligo(ethylene glycol) were installed via postpolymerization thiol-ene reactions. These degradable polymers were then employed as excipients for the stabilization of the therapeutic protein granulocyte colony-stimulating factor (G-CSF) against storage at 4 °C and shipping temperatures of 60 °C. The best stabilization was observed using the trehalose- and zwitterion- substituted polyesters. Both the trehalose- and carboxybetaine-substituted pCL were further investigated with regard to molecular weight dependence, and it was found that the molecular weight was minimally important for stabilization to refrigeration, but critical for G-CSF stabilization at elevated temperatures. Both high performing zwitterionic and trehalose polyesters were also degraded, and the polymers and degradation products were shown to be noncytotoxic. This work provides potential biocompatible polymers for stabilization of the important therapeutic G-CSF, as well as a general platform for the future discovery of new polymeric protein stabilizers.

Dataset Information

Allicin Induces Thiol Stress in Bacteria through S-Allylmercapto Modification of Protein Cysteines.

Publications

Allicin Induces Thiol Stress in Bacteria through S-Allylmercapto Modification of Protein Cysteines.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets