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 (Cu 2+ ).
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