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The growing threat of antibiotic-resistant bacteria necessitates the development of alternative antimicrobial strategies. This study investigated the design and evaluation of novel photodynamic agents based on Rose Bengal (RB) conjugated to two plant lectins, Pisum sativum agglutinin (PSA) and Laburnum anagyroides agglutinin (LABA), for targeted photodynamic inactivation of Gram-positive and Gram-negative bacteria. Both conjugates demonstrated high singlet oxygen quantum yields compared with free RB. Antibacterial efficacy was assessed against methicillin-sensitive and methicillin-resistant Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Salmonella paratyphi B under white LED illumination. PSA-RB exhibited superior bactericidal activity against all strains, whereas LABA-RB showed strain-specific efficacy, particularly against Gram-negative species. A binary mixture of PSA-RB and LABA-RB synergistically inactivated both MSSA and MRSA at RB concentrations of 6–10 nM and light doses of 3.1–7.8 J/cm2. Complete killing of E. coli and S. paratyphi B was achieved at approximately half the RB concentrations needed for individual conjugates. PSA-RB activity primarily drove the inactivation of P. aeruginosa. Uptake studies revealed significantly enhanced accumulation of lectin-conjugated RB compared to free RB, with synergistic uptake observed for the conjugate mixture. These results suggest that lectin-based RB conjugates are effective antibacterial agents for photodynamic treatment, especially via the dual-targeting method.

To the best of our knowledge, this is the first attempt to synthesize, characterize, and determine the antibacterial and anticancer effects of three novel conjugates of plant lectins: phytohemagglutinin lectin (PHA), soybean agglutinin (SBA), and peanut agglutinin (PNA) with chitosan nanoparticles (CHNPs). The lectin concentration within prepared conjugates was estimated using nannodrop, and the highest concentration was 0.96 mg/ml in PHA-CHNPs. SDS-PAGE showed the molecular weights of conjugates ranged from 26.9 to 63.9 kDa. UV spectrophotometer recorded the absorbance peaks of conjugates somewhere between 200 and 230 nm. Hemagglutination analysis verified the presence of actively binding lectins. The three conjugates showed strong antibacterial activity against Gram-positive and Gram-negative bacteria compared to pure lectins and chitosan nanoparticles. The highest inhibition zone was 55.67 ± 4.04, 38.67 ± 5.51, and 37.33 ± 2.52 for PHA-CHNPs against Enterococcus faecalis , Salmonella typhimurium , and Shigella sonnei , respectively, followed by 36.3 ± 0.15 for PNA-CHNPs against Staphylococcus aureus . The lowest MIC was 1.5 µg/ml for PHA-CHNPs against Enterococcus faecalis , followed by 12 µg/ml for PNA-CHNPs and SBA-CHNPs against Salmonella typhimurium and Enterococcus faecalis , respectively. TEM microphotographs show the conjugation pattern between lectins and chitosan nanoparticles and the morphological differences between control, treated bacteria, and cancer cells. Moreover, 100 μg/ml of PHA-CHNPs affect tongue carcinoma (HNO-97), colorectal cancer (HT-29), and human melanoma (A375) cancer cell lines, reducing cell viability by 38.78 ± 1.85%, 49.88 ± 1.11%, and 66.92 ± 3.60%, respectively. This study develops three innovative conjugates of lectin chitosan nanoparticles that need to be tested as potential antibacterial and anticancer agents for medical and cancer therapy applications. Key points • Lectin-conjugated chitosan nanoparticles exhibit antibacterial activity. • All conjugates are safe for oral epithelial cells and human skin fibroblasts. • The PHA-CHNP conjugates have anticancer activity against HNO-97, HT-29, and A375.

Algal lectin Griffithsin (GRFT) is a well-known mannose-binding protein which has broad-spectrum antiviral activity against several important infectious viruses including HIV, HCV, and SARS-CoV-2. Therefore, GRFT has been brought great attention to antiviral therapeutic development. In this report, we have tested GRFT’s activity against the lethal Ebola virus in vitro and in vivo. Our data have shown that the IC50 value is about 42 nM for inhibiting Zaire Ebola virus (EBOV) infection in vitro. The preliminary in vivo mice model using mouse-adapted EBOV has also shown a certain efficacy for delayed mortality compared to the control animals. A GRFT pull-down experiment using viral particles demonstrates that GRFT can bind to N-glycans of EBOV. Thus, it can be concluded that GRFT, through binding to viral glycans, may block Ebola virus infection and has potential for the treatment of Ebola virus disease (EVD).

Lectins are proteins that reversibly bind to carbohydrates and are commonly found across many species. The Banana Lectin (BanLec) is a member of the Jacalin-related Lectins, heavily studied for its immunomodulatory, antiproliferative, and antiviral activity. In this study, a novel sequence was generated in silico considering the native BanLec amino acid sequence and 9 other lectins belonging to JRL. Based on multiple alignment of these proteins, 11 amino acids of the BanLec sequence were modified because of their potential for interference in active binding site properties resulting in a new lectin named recombinant BanLec-type Lectin (rBTL). rBTL was expressed in E. coli and was able to keep biological activity in hemagglutination assay (rat erythrocytes), maintaining similar structure with the native lectin. Antiproliferative activity was demonstrated on human melanoma lineage (A375), evaluated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT). rBTL was able to inhibit cellular growth in a concentration-dependent manner, in an 8-h incubation, 12 µg/mL of rBTL led to a 28.94% of cell survival compared to cell control with 100%. Through a nonlinear fit out log-concentration versus biological response, an IC50% of 3.649 µg/mL of rBTL was determined. In conclusion, it is possible to state that the changes made to the rBTL sequence maintained the structure of the carbohydrate-binding site without changing specificity. The new lectin is biologically active, with an improved carbohydrate recognition spectrum compared to nBanLec, and can also be considered cytotoxic for A375 cells.

We have isolated a novel lectin, named HRL40 from the green alga Halimeda renschii. In hemagglutination-inhibition test and oligosaccharide-binding experiment with 29 pyridylaminated oligosaccharides, HRL40 exhibited a strict binding specificity for high-mannose N-glycans having an exposed (α1-3) mannose residue in the D2 arm of branched mannosides, and did not have an affinity for monosaccharides and other oligosaccharides examined, including complex N-glycans, an N-glycan core pentasaccharide, and oligosaccharides from glycolipids. The carbohydrate binding profile of HRL40 resembled those of Type I high-mannose specific antiviral algal lectins, or the Oscillatoria agardhii agglutinin (OAA) family, which were previously isolated from red algae and a blue-green alga (cyanobacterium). HRL40 potently inhibited the infection of influenza virus (A/H3N2/Udorn/72) into NCI-H292 cells with half-maximal effective dose (ED50) of 2.45 nM through high-affinity binding to a viral envelope hemagglutinin (KD, 3.69 × 10−11 M). HRL40 consisted of two isolectins (HRL40-1 and HRL40-2), which could be separated by reverse-phase HPLC. Both isolectins had the same molecular weight of 46,564 Da and were a disulfide -linked tetrameric protein of a 11,641 Da polypeptide containing at least 13 half-cystines. Thus, HRL40, which is the first Type I high-mannose specific antiviral lectin from the green alga, had the same carbohydrate binding specificity as the OAA family, but a molecular structure distinct from the family.

Background: The consumption of kiwifruit (Actinidia deliciosa var. Hayward) is recognized for its health benefits due to its high vitamin C content and bioactive secondary metabolites, such as phenolic compounds with antioxidant properties. These compounds may help prevent chronic noncommunicable diseases, currently the leading cause of death. Additionally, plants and fruits contain proteins like lectins, which contribute to plant defense and may also have health-promoting effects, including antitumor and hypoglycemic activities. Objectives: The objective of this work was to evaluate and identify the phenolic compounds in this variety of kiwifruit, as well as to investigate the lectin activity and the potential dietary benefits of this combination. Methods: This study quantified and identified total phenolic compounds and flavonoids in a kiwifruit extract using HPLC-DAD-MS/MS, and assessed their antioxidant activity through the DPPH method. Results: Novel lectin activity was also investigated, with polypeptide characterization and glycoprotein profiling performed. The affinity of lectins for glycans was evaluated using a hemagglutination inhibition assay. Results indicated that kiwifruit lectins bind to glycoreceptors on tumor cell membranes, with a specific affinity for sialic acid, an important glycan in tumor-associated glycomic aberrations. Conclusions: These findings suggest that the bioactive components of kiwifruit may offer multiple health benefits through a synergistic effect.

Natural-product derived lectins can function as potent viral inhibitors with minimal toxicity as shown in vitro and in small animal models. We here assessed the effect of rectal application of an anti-HIV lectin-based microbicide Q-Griffithsin (Q-GRFT) in rectal tissue samples from rhesus macaques. E-cadherin + cells, CD4 + cells and total mucosal cells were assessed using in situ staining combined with a novel customized digital image analysis platform. Variations in cell numbers between baseline, placebo and Q-GRFT treated samples were analyzed using random intercept linear mixed effect models. The frequencies of rectal E-cadherin + cells remained stable despite multiple tissue samplings and Q-GRFT gel (0.1%, 0.3% and 1%, respectively) treatment. Whereas single dose application of Q-GRFT did not affect the frequencies of rectal CD4 + cells, multi-dose Q-GRFT caused a small, but significant increase of the frequencies of intra-epithelial CD4 + cells (placebo: median 4%; 1% Q-GRFT: median 7%) and of the CD4 + lamina propria cells (placebo: median 30%; 0.1–1% Q-GRFT: median 36–39%). The resting time between sampling points were further associated with minor changes in the total and CD4 + rectal mucosal cell levels. The results add to general knowledge of in vivo evaluation of anti-HIV microbicide application concerning cellular effects in rectal mucosa.

Interactions between endothelial selectins and the leukocyte counter-receptor PSGL1 mediates leukocyte recruitment to inflammation sites. PSGL1 is highly sialylated, making it a potential ligand for Siglec-5, a leukocyte-receptor that recognizes sialic acid structures. Binding assays using soluble Siglec-5 variants (sSiglec-5/C4BP and sSiglec-5/Fc) revealed a dose- and calcium-dependent binding to PSGL1. Pre-treatment of PSGL1 with sialidase reduced Siglec-5 binding by 79 ± 4%. In confocal immune-fluorescence assays, we observed that 50% of Peripheral Blood Mononuclear Cells (PBMCs) simultaneously express PSGL1 and Siglec-5. Duolink-proximity ligation analysis demonstrated that PSGL1 and Siglec-5 are in close proximity (<40 nm) in 31 ± 4% of PBMCs. In vitro perfusion assays revealed that leukocyte-rolling over E- and P-selectin was inhibited by sSiglec-5/Fc or sSiglec-5/C4BP, while adhesion onto VCAM1 was unaffected. When applied to healthy mice (0.8 mg/kg), sSiglec-5/C4BP significantly reduced the number of rolling leukocytes under basal conditions (10.9 ± 3.7 versus 23.5 ± 9.3 leukocytes/field/min for sSiglec-5/C4BP-treated and control mice, respectively; p  = 0.0093). Moreover, leukocyte recruitment was inhibited over a 5-h observation period in an in vivo model of TNFalpha-induced inflammation following injection sSiglec-5/C4BP (0.8 mg/kg). Our data identify PSGL1 as a ligand for Siglec-5, and soluble Siglec-5 variants appear efficient in blocking PSGL1-mediated leukocyte rolling and the inflammatory response in general.

Lectins are proteins that specifically recognize carbohydrates on cell membranes, triggering several cellular events such as apoptosis of cancer-transformed cells; however, the mechanisms of action remain incompletely understood. Our research group has reported that a concentrated fraction of Tepary bean lectins (Phaseolus acutifolius; TBLF) exhibits the concentration-dependent induction of apoptosis in colon cancer cells by caspase activation. It is well established that an increase in cytoplasmic calcium ([Ca2+]i) initiates intracellular signals involved in processes such as exocytosis, gene transcription, apoptosis, cell cycle regulation, and muscle contraction, among others. Furthermore, dysregulated calcium signaling has been implicated in various diseases, including certain neurological disorders and cancer. In this study, we aim to demonstrate the effects of native TBLF lectins and a recombinant lectin (rTBL-1) on calcium mobility in breast cancer cells (MCF-7) and non-cancerous cells (MCF-12F). Both TBLF and rTBL-1 increased intracellular calcium concentrations and mobilized calcium from intracellular stores in a concentration-dependent manner; however, the two cell lines exhibited differential responses. While MCF-12F cells restored cytoplasmic calcium concentration, MCF-7 cells maintained a high intracellular calcium concentration. This strongly suggests that lectins can elicit differential cellular responses in cancer and non-cancer cells due to variations in their intrinsic mechanisms of calcium homeostasis. Finally, we demonstrated that TBLF and rTBL-1 can differentially alter Metabolic Cellular Activity (MCA) as a direct measure of cell viability (CVi) in both cell lines. These findings strengthen the evidence of the therapeutic potential of Tepary bean lectins. Undoubtedly, further studies will be necessary to elucidate the mechanisms underlying their applications.

Garlic has long been used as an antimicrobial spice and herbal remedy. The aim of this study was to isolate the antimicrobial agent in garlic water extract against Staphylococcus aureus ( S. aureus ) and investigate its antimicrobial mechanism. By an activity-guided separation, garlic lectin-derived peptides (GLDPs) with main molecular weight of around 12 kDa were extracted by liquid nitrogen grinding and identified with high bactericidal activity toward S. aureus , and the MIC was determined as 24.38 μg/mL. In-gel digestion-based proteomic analysis indicated that the peptide sequences were highly identical to the B strain of garlic protein lectin II. Structure analysis suggested that the secondary structure was strongly affected by lyophilization and thus resulted in the inactivation of GLDPs ( P  < 0.05). Mechanism study revealed that treatment of GLDPs resulted in cell membrane depolarization in a dose-dependent manner, and the disruptions of the cell wall and membrane integrities were observed under electric microscopies. GLDPs could successfully dock with cell wall component lipoteichoic acid (LTA) via van der Waals and conventional bonds in molecular docking analysis. These results suggested that GLDPs were responsible for the S. aureus targeting activity and might be promising candidates for antibiotic development against bacterial infection.