D-Histidine

D-Histidine is an anti-biofilm agent that targets bacterial quorum sensing systems (such as RhlI/RhlR pathway) and has antibacterial activity. D-Histidine works by non-covalently binding to bacterial regulatory factors or copper ion complexes, selectively inhibiting bacterial biofilm formation and motility. D-Histidine downregulates quorum sensing-related gene expression, reduces the synthesis of virulence factors (such as alginate and proteases), and interferes with bacterial membrane stability, inhibiting biofilm formation, promoting the disintegration of mature biofilms, and enhancing antibiotic sensitivity. D-Histidine is also an efficient catalyst for the salt-induced peptide formation (SIPF) reaction, which promotes the condensation of amino acids to form dipeptides (such as dialanine and dilysine) by forming a complex with copper ions (Cu²⁺)^[1][2][3]. In Vitro:D-Histidine (100 mM; 24 h) significantly inhibited biofilm formation and promoted the disintegration of mature biofilm in the Pseudomonas aeruginosa PAO1 biofilm formation experiment. Crystal violet staining and laser confocal microscopy showed that the amount of biofilm was reduced by about 55%^[1].
D-Histidine (100 nM-100 mM; 24 h) downregulated RhlI/RhlR gene expression in a concentration-dependent manner in the quorum sensing (QS)-related gene expression experiment. At 100 mM, the expression levels of RhlI and RhlR genes decreased by about 80% and 90%, respectively^[1].
D-Histidine (2.5 mM) increases the production of di-alanine by 14-22 times compared to the absence of catalyst; for the lysine system, D-Histidine increases the catalytic effect about 2-3 times^[2].
In Vivo:Oxygen free radicals are associated with traumatic brain injury and brain edema (BE). For example, hydroxyl free radicals can induce lipid peroxidation, thereby generating lipid free radicals that may be an important source of singlet oxygen.
In the rat cryoinjury model, only L-histidine (HY-N0832) (100 mg/kg; intravenous injection; injection 30 min before injury) has singlet oxygen scavenger activity compared with D-histidine, and L-histidine reduces brain edema in rats after cryoinjury^[3].