The NOX Family of Proteins Is Also Present in Bacteria

• Main Authors: Christine Hajjar, Mickael V. Cherrier, Gaetan Dias Mirandela, Isabelle Petit-Hartlein, Marie José Stasia, Juan C. Fontecilla-Camps, Franck Fieschi, Jéérééôme Dupuy, Richard Gerald Brennan
• Format: Article
• Language: English
• Published: American Society for Microbiology 2017-11-01
• Series: mBio
• Online Access: http://mbio.asm.org/cgi/content/full/8/6/e01487-17

Transmembrane NADPH oxidase (NOX) enzymes have been so far only characterized in eukaryotes. In most of these organisms, they reduce molecular oxygen to superoxide and, depending on the presence of additional domains, are called NOX or dual oxidases (DUOX). Reactive oxygen species (ROS), including superoxide, have been traditionally considered accidental toxic by-products of aerobic metabolism. However, during the last decade it has become evident that both O2•− and H2O2 are key players in complex signaling networks and defense. A well-studied example is the production of O2•− during the bactericidal respiratory burst of phagocytes; this production is catalyzed by NOX2. Here, we devised and applied a novel algorithm to search for additional NOX genes in genomic databases. This procedure allowed us to discover approximately 23% new sequences from bacteria (in relation to the number of NOX-related sequences identified by the authors) that we have added to the existing eukaryotic NOX family and have used to build an expanded phylogenetic tree. We cloned and overexpressed the identified nox gene from Streptococcus pneumoniae and confirmed that it codes for an NADPH oxidase. The membrane of the S. pneumoniae NOX protein (SpNOX) shares many properties with its eukaryotic counterparts, such as affinity for NADPH and flavin adenine dinucleotide, superoxide dismutase and diphenylene iodonium inhibition, cyanide resistance, oxygen consumption, and superoxide production. Traditionally, NOX enzymes in eukaryotes are related to functions linked to multicellularity. Thus, the discovery of a large family of NOX-related enzymes in the bacterial world brings up fascinating questions regarding their role in this new biological context.