Inhibitory effects of nitrite and sulfite/peroxymonosulfate on bacteria are mediated respectively through respiration and intracellular GSH homeostasis

As nitrite, sulfite has been used in food preservation for centuries but how it inhibits bacterial growth remains underexplored. To address this issue, in this study, we set out to test if cytochrome (cyt) c proteins protect bacteria from the damage of certain reactive sulfur species (RSS) because they do so in the case of reactive nitrogen species (RNS). We show that some reactive sulfur species, such as sulfite and peroxymonosulfate (PMS), inhibit growth of bacterial strains devoid of cytochrome (cyt) c proteins. Subsequent investigations link the inhibition of sulfite/PMS to activity of cbb₃-type heme-copper oxidase (cbb₃-HCO). However, in vitro comparative analysis rules out that either cbb₃-HCO or cyt bd oxidase is the primary target of sulfite/PMS. Instead, we found that sulfite/PMS and the cbb₃-HCO loss regulate intracellular redox status in a similar manner, by affecting GSH/GSSG homeostasis. The link between the GSH/GSSG homeostasis and sulfite/PMS is further substantiated by using the mutants with enhanced GSSG generation. Furthermore, we present the data to show that inhibitory effects of nitrite and sulfite/PMS are additive although the overall effects may vary depending on species. Our results open an avenue to control bacteria by developing more robust agents that modulating intracellular redox status, which may be used in combination with nitrite as a promising antimicrobial strategy.