The NOX Family of Proteins Is Also Present in Bacteria.

Christine Hajjar,Isabelle Petit-Hartlein,Gaëtan Dias Mirandela,Marie José Stasia,Mickaël V Cherrier,Franck Fieschi,Juan C Fontecilla-Camps,Jérôme Dupuy,Richard Gerald Brennan

doi:10.1128/mbio.01487-17

Abstract

ABSTRACTTransmembrane 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.

Highlights

Transmembrane NADPH oxidase (NOX) enzymes have been so far only characterized in eukaryotes
Besides NOX2, which is found in phagocytes, cardiac tissue and brain, where it is involved in host defense, muscle contraction, and neural degeneration, respectively [20], NOX enzymes from nonimmune tissues are involved in processes such as cell proliferation, apoptosis, and receptor signaling [3]
DISCUSSION new members of the NOX family of electron transfer membrane proteins have been continuously discovered since the 2000s, they have been restricted to eukaryotic organisms, from fungi to animals and plants

Summary

Introduction

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). Free radicals are normally generated in the human body by metabolic processes, the best known being superoxide, peroxide, and radical hydroxyl oxygen species, which are collectively called reactive oxygen species (ROS) These species, which are highly reactive and can attack proteins, lipids, and nucleic acids, are major contributors to damage in biological organisms [1]. In addition to ROS-provoked damage, deregulation of NOX-dependent ROS production can have pathological consequences related to a specific physiological context (e.g., chronic granulomatous disease, autoimmune disorders, hypothyroidism when ROS production is impaired, or cardiovascular and neurodegenerative diseases in the case of ROS overproduction) [21, 23]

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