Cytochrome bd and bacterial respiration in sulfide rich environments

Cytochrome bd is a prokaryotic respiratory terminal oxidase phylogenetically unrelated to haem-copper oxidases. In addition to sustaining energy metabolism, this enzyme is implicated in bacterial protection against oxidative and nitrosative stress. Cytochrome bd is only found in prokaryotes and, as it promotes virulence in several pathogenic bacteria, it is currently recognized as a potential drug target. Escherichia coli and other microbes, including pathogens, colonize the human gut, that is known to be rich in hydrogen sulfide (H2S), while being a major site of reactive nitrogen species production. Depending on its concentration, H2S can have beneficial or detrimental effects in both prokaryotes and eukaryotes. Among the most well known toxic effects of H2S is the inhibition of cellular respiration due to binding to mitochondrial heme copper-type cytochrome c oxidase. Interestingly, working on E. coli mutant strains and purified proteins, we found that bd-type oxidases are insensitive to H2S inhibition, thereby promoting bacterial respiration and growth in the presence of high levels of H2S . The potential impact of this discovery on human (patho)physiology and its possible applications in the field of infectious diseases will be discussed.