NAD+-targeting by bacteria: an emerging weapon in pathogenesis

Abstract

Nicotinamide adenine dinucleotide (NAD+) is a major cofactor in redox reactions in all life-forms. A stable level of NAD+ is vital to ensure cellular homeostasis. Some pathogens can modulate NAD+ metabolism to their advantage and even utilize or cleave NAD+ from the host using specialized effectors known as ADP-ribosyltransferase toxins and NADases, leading to energy store depletion, immune evasion or even cell death. This review explores recent advances in the field of bacterial NAD+-targeting toxins, highlighting the relevance of NAD+ modulation as an emerging pathogenesis strategy. In addition, we discuss the role of specific NAD+-targeting toxins in niche colonization and bacterial lifestyle as components of toxin/antitoxin systems and key players in interbacterial competition. Understanding the mechanisms of toxicity, regulation and secretion of these toxins will provide interesting leads in the search for new antimicrobial treatments in the fight against infectious diseases.

Keywords: ADP-ribosylation; NAD+; NADase; bacterial virulence factor; immune response evasion; secretion pathway.