Muramyl dipeptide (MDP) is the smallest peptidoglycan fragment able to trigger the immune response. Structural modification of MDP can lead to the preparation of analogs with improved immunostimulant properties, including desmuramyl peptides (DMPs). The aim of this work was to prepare the desmuramyl peptide (L-Ala-D-Glu)-containing adamantyl-triazole moiety and its mannosylated derivative in order to study their immunomodulatory activities in vivo. The adjuvant activity of the prepared compounds was evaluated in a murine model using ovalbumin as an antigen, and compared to the reference adjuvant ManAdDMP. The results showed that the introduction of the lipophilic adamantyl-triazole moiety at the C-terminus of L-Ala-D-Glu contributes to the immunostimulant activity of DMP, and that mannosylation of DMP modified with adamantyl-triazole causes the amplification of its immunostimulant activity.

Background/Objectives: FimH adhesin, located at the tips of type 1 pili in Escherichia coli (E. coli), plays a crucial role in bacterial adhesion to the surface urothelial cells—a key step in the pathogenesis of urinary tract infections (UTIs). Given the rising concern over antimicrobial resistance (AMR), and considering that E. coli is one of the pathogens with the largest AMR burdens on a global scale, alternative strategies targeting bacterial adhesion are gaining increasing attention. Products that contain D-mannose and cranberry-derived phenolic compounds have shown promise in preventing E. coli colonization and infection. The aim of this study was to investigate the antiadhesive effects of cranberry-related phenolic compounds on FimH-mediated E. coli adhesion using a cellular hemagglutination inhibition assay, as well as to assess the synergistic effects of mannose and phenolic compounds on biofilm formation. Methods: A range of phenolic acids (benzoic, chlorogenic, hippuric, p-coumaric, ferulic and caffeic), resveratrol, (+)-catechin and procyanidin A, as well as a Vaccinium macrocarpon extract, were evaluated for their ability to inhibit FimH-mediated adhesion. A binocular microscope was used to observe agglutination, and we also evaluated the biofilm inhibition potential of the phenolic compounds in the presence of D-mannose. Results: Our results demonstrated that these compounds significantly reduced hemagglutination, with benzoic acid, chlorogenic acid, caffeic acid and resveratrol exhibiting strong inhibitory effects at concentrations as low as 0.25 mM. Furthermore, the addition of 1 mM solutions of these phenolic compounds to D-mannose resulted in a twofold reduction in the inhibition titer, suggesting synergistic interactions. In addition to their antiadhesive properties, the tested phenolic compounds contributed slightly to the inhibition of FimH-mediated biofilm formation, further supporting their potential roles in UTI prevention. Conclusions: These findings highlight the potential of cranberry-derived phenolics as natural antiadhesive agents against E. coli and warrant further investigation into their mechanisms of action and possible applications in infection control.

Muramyl dipeptide (N-acetylmuramyl-L-alanyl-D-isoglutamine, MDP) is the smallest peptidoglycan fragment able to trigger an immune response by activating the NOD2 receptor. Structural modification of MDP can lead to analogues with improved immunostimulating properties. The aim of this work was to prepare mannosylated desmuramyl peptides (ManDMP) containing lipophilic triazole substituents to study their immunomodulating activities in vivo. The adjuvant activity of the prepared compounds was evaluated in the mouse model using ovalbumin as an antigen and compared to the MDP and referent adjuvant ManDMPTAd. The obtained results confirm that the α-position of D-isoGln is the best position for the attachment of lipophilic substituents, especially adamantylethyl triazole. Compound 6c exhibited the strongest adjuvant activity, comparable to the MDP and better than referent ManDMPTAd.