The increasing prevalence of antimicrobial resistance and biofilm-associated infections has intensified the search for alternative anti-infective strategies. Short peptide-based molecules have attracted growing interest due to their structural simplicity, biocompatibility, and multifunctional biological properties. In this study, the antimicrobial and antibiofilm activities of two dipeptides, glycyl–histidine and methionyl–glycine, were evaluated against reference microorganisms, including Escherichia coli ATCC 35218, Klebsiella pneumoniae MTCC 109, Pseudomonas aeruginosa ATCC 27853, Staphylococcus aureus ATCC 25923, and Candida albicans ATCC 10231. Antimicrobial activity was determined using broth microdilution and disk diffusion assays, while antibiofilm effects were evaluated at sub-inhibitory concentrations using a crystal violet-based biofilm inhibition assay supported by light microscopy. In addition, the electronic structure, binding interactions, and pharmacokinetic properties of the dipeptides were investigated using integrated density functional theory (DFT), molecular docking, and ADME analyses. Glycyl–histidine exhibited antimicrobial activity against all tested bacterial strains (MIC: 12.5 mg/mL) and against C. albicans (MIC: 50 mg/mL), whereas methionyl–glycine showed no detectable antimicrobial activity. Both dipeptides demonstrated microorganism-dependent antibiofilm effects, with glycyl–histidine consistently displaying stronger activity. Notably, glycyl–histidine reduced biofilm formation by up to 88% in K. pneumoniae and by 54% in P. aeruginosa at 0.5 × MIC. In C. albicans, biofilm formation decreased by 22–39% under conditions where the reference antibiotic solution showed no antibiofilm effect. Computational analyses supported the experimental findings and provided molecular-level insights into the antimicrobial and antibiofilm potential of glycyl–histidine. Overall, these results identify glycyl–histidine as a promising anti-infective dipeptide and highlight its potential as a promising building block for the development of novel anti-infective agents.
Şahal et al. (Wed,) studied this question.