Antimicrobial garlic-derived diallyl polysulfanes: Interactions with biological thiols in Bacillus subtilis

Diallylpolysulfanes are the key constituents of garlic oils, known to exhibit broad spectrum anticancer and antimicrobial activity. Studies in vitro, and in mammalian cells, have shown they react, via thiol-polysulfane exchange, with their major low molecular weight thiol, glutathione. However, there are no detailed reports of diallylpolysulfane effects on other common thiol metabolites (cysteine and coenzyme A) or major thiol cofactors (e.g. bacillithiol) that many Gram positive bacteria produce instead of glutathione. Diallylpolysulfanes were individually purified then screened for antimicrobial activity against Bacillus subtilis. Their impact on thiol metabolites (bacillithiol, cysteine, coenzyme A, protein thiols allyl thiols//persulfides) in B. subtilis cultures were analysed, by HPLC. Diallylpolysulfane bioactivity increased with increasing chain length up to diallyltetrasulfane, but then plateaued. Within two minutes of treating B. subtilis with diallyltrisulfane or diallyltetrasulfane intracellular bacillithiol levels decreased by ~90%. Cysteine and CoA were also affected but to a lesser degree. This was accompanied by the accumulation of allyl thiol and allyl persulfide. A significant level of protein-S-allylation was also detected. In addition to the major low molecular weight thiol, diallylpolysulfanes can also have an impact on other thiol metabolites and protein thiols. This study shows the rapid parallel impact of polysulfanes on different biological thiols inside Bacillus subtilis alongside the concomitant generation of allyl thiols and persulfides. [Display omitted] •Antibacterial activity of diallylpolysulfanes peaks at the diallylpentasulfide•Diallylpolysulfanes rapidly deplete bacillithiol in Bacillus subtilis.•Intracellular allyl thiol and allylpersulfide is also produced.•Protein thiols also appear to be modified by diallylpolysulfanes