Redox regulation in host-pathogen interactions: thiol switches and beyond

Our organism is exposed to pathogens on a daily basis. Owing to this age-old interaction, both pathogen and host evolved strategies to cope with these encounters. Here, we focus on the consequences of the direct encounter of cells of the innate immune system with bacteria. First, we will discuss the bacterial strategies to counteract powerful reactive species. Our emphasis lies on the effects of hypochlorous acid (HOCl), arguably the most powerful oxidant produced inside the phagolysosome of professional phagocytes. We will highlight individual examples of proteins in gram-negative bacteria activated by HOCl via thiol-disulfide switches, methionine sulfoxidation, and N- chlorination of basic amino acid side chains. Second, we will discuss the effects of HOCl on proteins of the host. Recent studies have shown that both host and bacteria address failing protein homeostasis by activation of chaperone-like holdases through N-chlorination. After discussing the role of individual proteins in the HOCl-defense, we will turn our attention to the examination of effects on host and pathogen on a systemic level. Recent studies using genetically encoded redox probes and redox proteomics highlight differences in redox homeostasis in host and pathogen and give first hints at potential cellular HOCl signaling beyond thiol- disulfide switch mechanisms.

Automated summary

The study focuses on the direct encounter between cells of the innate immune system and bacteria, discussing strategies used by both pathogens and hosts to cope with reactive species, as well as the effects of HOCl on host and bacterial proteins. Recent research utilizing genetically encoded redox probes and redox proteomics highlights differences in redox homeostasis between hosts and pathogens.