Physiological Roles of Nitrite and Nitric Oxide in Bacteria: Similar Consequences from Distinct Cell Targets,...

Nitrite and nitric oxide (NO) are two active nitrogen oxides that display similar biochemical properties, especially when interacting with redox-sensitive proteins (i.e., hemoproteins), an observation serving as the foundation of the notion that the antibacterial effect of nitrite is largely attributed to NO formation. However, a growing body of evidence suggests that they are largely treated as distinct molecules by bacterial cells. Although both nitrite and NO are formed and decomposed by enzymes participating in the transformation of these nitrogen species, NO can also be generated via amino acid metabolism by bacterial NO synthetase and scavenged by flavohemoglobin. NO seemingly interacts with all hemoproteins indiscriminately, whereas nitrite shows high specificity to heme-copper oxidases. Consequently, the homeostasis of redox-sensitive proteins may be responsible for the substantial difference in NO-targets identified to date among different bacteria. In addition, most protective systems against NO damage have no significant role in alleviating inhibitory effects of nitrite. Furthermore, when functioning as signal molecules, nitrite and NO are perceived by completely different sensing systems, through which they are linked to different biological processes.