Arginine at the host-pathogen interface

Nutrient availability shapes the course of infection. Arginine, a conditionally essential amino acid, plays a crucial role in both host immune defense and pathogen metabolism. As a precursor for nitric oxide production, arginine supports immune functions in multiple immune cell types to control infections. However, it also serves as a signal for pathogens that promotes bacterial survival and growth. A plethora of recent studies have shown that arginine functions not only as a metabolic substrate but also as a key environmental cue that can alter cyclic diguanylate levels. Arginine availability regulates multiple bacterial processes in both Gram-positive and Gram-negative species including toxin production, biofilm formation, Type III secretion system, swarming, persistence, and immune evasion. In this way, arginine levels can shape how pathogens behave within the host environment. This review examines how fluctuations in arginine levels across different host niches influence microbial pathogenesis and highlights the complex interplay between arginine availability and bacterial behavior. Understanding the role of arginine in host-pathogen interactions may provide new therapeutic strategies to combat infections by targeting bacterial responses to this crucial nutrient.