Interspecies comparison of the bacterial response to allicin reveals species-specific defense strategies

ABSTRACT: Allicin, a volatile diallylthiosulfinate from garlic (Allium sativum), exhibits broad-spectrum activity against microbial pathogens. It disrupts thiol and redox homeostasis, proteostasis, and cell membrane integrity leading to inactivation of even multidrug resistant strains. Since medicine demands cost-efficient antimicrobials with so far unexploited mechanisms, allicin with its multifaceted mode of action is a promising lead structure for future therapeutics. However, while progress is being made in fully unraveling its mode of action, little is known on bacterial adaptation strategies to cope with allicin-like stress. Some isolates of Pseudomonas aeruginosa and Escherichia coli, withstand exposure to higher allicin concentrations than other bacteria due to as yet unknown cellular mechanisms. To elucidate resistance and sensitivity-conferring cellular processes we compared the acute proteomic responses of the resistant species P. aeruginosa and sensitive species Bacillus subtilis to the published proteomic response of E. coli to allicin treatment. The cellular defense strategies shared functional features: proteins involved in protein (re)folding and repair, ROS and RSS detoxification, and cell envelope modification were upregulated. In both Gram-negative species, protein synthesis of up to 64% of the proteins synthesized in untreated cells was down-regulated while the sensitive, Gram-positive B. subtilis responded by upregulation of multiple regulons. A comparison of the B. subtilis proteomic response to a library of proteomic responses to antibiotic treatment, revealed 30 proteins specifically upregulated by allicin. Other upregulated proteins indicating oxidative stress were shared with nitrofurantoin and diamide. Microscopy-based assays further indicate that in B. subtilis cell wall integrity was impaired.

INSTRUMENT(S): Synapt MS

ORGANISM(S): Pseudomonas Aeruginosa Pao1 Bacillus Subtilis Subsp. Subtilis Str. 168

SUBMITTER: Christoph Senges  

LAB HEAD: Julia E. Bandow

PROVIDER: PXD012622 | Pride | 2021-03-09

REPOSITORIES: Pride