Arginine Regulates the Mucoid Phenotype of Hypervirulent .

Hypervirulent is associated with severe community-acquired infections. Hypervirulent colonies typically exhibit a mucoid phenotype. mucoidy is influenced by a complex combination of environmental factors and genetic mechanisms. Mucoidy results from altered capsular polysaccharide chain length, yet the specific environmental cues regulating this phenotype and their impact on pathogenesis remain unclear. This study demonstrates that casamino acids enhance the mucoidy phenotype but do not affect total capsular polysaccharide levels. Through targeted screening of each amino acid present in casamino acids, we identified that arginine is necessary and sufficient to stimulate the mucoid phenotype without altering capsule abundance. Furthermore, arginine activates the promoter, increasing transcript levels, which in turn modulates capsular polysaccharide chain length and diversity. The arginine regulator, ArgR, plays a pivotal role in this regulatory cascade since deleting decreases mucoidy and increases capsular polysaccharide chain length diversity. Additionally, the ∆ mutant displays increased macrophage association and has a substantial competitive defect in the lungs of mice, suggesting a link between arginine-dependent gene regulation, immune evasion and fitness. We discovered that arginine-dependent regulation of mucoidy is conserved in four additional hypervirulent isolates likely via a conserved ARG binding box present in promoters. Our findings support a model in which arginine activates ArgR and increases mucoidy in hypervirulent As a result, it is possible that arginine-dependent regulation of mucoidy allows hypervirulent to adapt the cell surface across different niches. This study underscores the significance of arginine as a regulatory signal in bacterial virulence.