Sandy F. van Vuuren

Quorum sensing (QS) is a bacterial communication mechanism that regulates collective behaviors such as virulence, motility, and biofilm formation. Consequently, materials capable of interacting with molecules associated with QS signaling pathways are of increasing interest as potential tools for studying and modulating bacterial communication processes. In this study, molecularly imprinted polymers (MIPs) were designed and synthesized using (R/S)-2,2-dimethyl-1,3-dioxolane-4-methanamine, an autoinducer-2 (AI-2)-inspired surrogate template to investigate molecular recognition of structures relevant to bacterial signaling systems. Five bulk MIPs were prepared by thermal radical polymerization using methacrylic acid, 4-vinylbenzoic acid, itaconic acid, trifluoromethacrylic acid, and acrylic acid as functional monomers. The resulting polymers were evaluated in terms of adsorption capacity, imprinting factor, and selectivity toward the template and structurally related compounds using liquid chromatography coupled with mass spectrometry (LC−MS)-based binding studies. Among the synthesized materials, the polymer prepared from methacrylic acid exhibited the highest specificity, with an imprinting factor of 3.10 at 50 μg L−1 and up to 19.14 at 2 μg L−1 of template concentrations, indicating strong concentration-dependent recognition. Computational modeling using density functional theory, molecular mechanics, and molecular dynamics simulations was employed to elucidate the molecular interactions governing template recognition and cavity formation. Theoretical analyses revealed that multiple hydrogen bonding, hydrophobic interactions, and electrostatic contacts contribute to stable analyte-polymer binding, supporting the experimentally observed selectivity. Selectivity experiments demonstrated preferential adsorption of the template and its closest structural analogue relative to several structurally related amine-containing compounds. Biological evaluation using the Chromobacterium violaceum model revealed that both molecularly imprinted and non-imprinted polymers reduced violacein production to varying degrees, indicating modulation of a QS-regulated phenotype under the experimental conditions employed. Collectively, these findings demonstrate the feasibility of using molecular imprinting strategies to generate polymeric materials capable of recognizing an AI-2-inspired surrogate template and influencing a QS-regulated biological response, highlighting their potential for development as innovative materials for antivirulence strategies against bacterial infections.

Global research has explored the antimicrobial properties of propolis; however, the antimycobacterial activity of South African (SA) propolis has been neglected. This study evaluated 109 propolis samples collected from eight SA provinces where the antimycobacterial activity, chemical composition and toxicity was evaluated. Samples were tested using a broth microdilution assay against various Mycobacterium strains ( M. fortuitum ATCC 6841, M. gordonae ATCC 14470 and M. smegmatis ATCC 14468) and the pathogenic M. tuberculosis H37Rv strain. A multi‐step approach combining ultra‐performance liquid chromatography/ mass spectrometry (UPLC–MS) profiling, high‐performance thin‐layer chromatography (HPTLC) bio‐autography, brine shrimp toxicity testing and molecular docking was employed on eight bio‐active and eight non‐active propolis samples. Two samples (GP68 and EC77B) demonstrated promising activity, with MICs ranging from 49–195 µg/mL against non‐tuberculous strains and 125 µg/mL against M. tuberculosis . Chemometric and bio‐autography analyses identified flavonoids and related compounds, including pinocembrin, galangin, chrysin and pinobanksin compounds as major contributors to activity. Both samples were non‐toxic at concentrations (1 mg/mL at 24 h; 0.5 mg/mL at 48 h). Molecular docking indicated favourable binding to key M. tuberculosis targets involved in cell wall biosynthesis (DprE1) and transcription (RNAP). This study demonstrates that selected SA‐derived propolis samples show strong antimycobacterial potential.

Objectives: The effectiveness of current treatments for vaginal infections is declining due to rising bacterial and yeast resistance, along with adverse effects on the vaginal microbiome. Although essential oils are known for their antimicrobial properties, their potential in treating vaginal infections either as monotherapies or in combination has not been thoroughly explored. Methods: This study assessed the antimicrobial efficacy (minimum inhibitory concentrations and biofilm inhibition) and toxicity of 46 essential oils and 86 combinations against both pathogens and beneficial vaginal microbiota ( Lactobacilli spp.). Results: Among the essential oils, Coriandrum sativum showed the most promising broad-spectrum antimicrobial activity (values as low as 0.13 mg/mL). Origanum vulgare and Myrtus communis were also of interest, having no toxicity with minimal impact on the vaginal biome ( Lactobacilli spp.). The combination of Cinnamomum camphora and Melaleuca cajuputi essential oil demonstrated superior antimicrobial inhibition (ΣFIC values 0.08-0.35), was non-toxic at both 24 and 48 hr (percentage inhibition of 34.34 ± 6.49 and 46.90 ± 0.79, respectively), and was able to inhibit Candida biofilms. Conclusion: These findings suggest that selected essential oils have potential as alternative treatments for vaginal infections, with the ability to inhibit vaginal pathogens, demonstrate low toxicity while not inhibiting the natural microbiota in vitro.

The synthesis of racemic isochromans from cashew nut shell liquid (CNSL) derived anacardic acids is described. Two key steps for the synthesis of the isochromans were utilized. (i) The benzylic bromination of methyl 2‐methoxy‐6‐pentadecylbenzoate was accomplished with N‐bromosuccinimide in the green solvent tert‐butyl acetate to afford methyl 2‐methoxy‐6‐(pentadec‐1‐en‐1‐yl)benzoate. (ii) Exposure of the secondary alcohol 1‐(2‐methoxy‐6‐(pentadec‐1‐en‐1‐yl)phenyl)ethanol to potassium tert‐butoxide resulted in the formation of the isochroman, trans‐8‐methoxy‐1‐methyl‐2‐tridecylisochroman. In a similar manner, the related isochroman, trans‐8‐methoxy‐1,3‐dimethylisochroman, could be synthesized. Selected antifungal and antibacterial testing showed moderate activities.

Honey has been revered for its medicinal properties for thousands of years, with medicinal uses including treating inflammation and gastric ulcers. The gut pathogen Helicobacter pylori is known to cause inflammation and gastric ulcers. Current treatment options for infection with H. pylori present several concerns due to the rapid gain in resistance and dysbiosis caused to the gut microbiome. While the anti‐ H. pylori properties of honey have been studied globally, a comprehensive range of southern African honeys has yet to be explored against this pathogen. This study is aimed at investigating South African honey for its anti‐ H. pylori activity and interaction with gut microbiome species. A total of 76 raw honey samples derived from South African apiarists were investigated, along with Manuka honey included for comparison. The anti‐ H. pylori activity and interaction with the gut microbiome species were assessed using the minimum inhibitory concentration (MIC) agar dilution assay. The hydrogen peroxide (H ₂ O ₂ ) concentration of antimicrobially active samples was determined using colorimetric test strips. A third of the investigated honeys showed activity comparable with that of Manuka honey. Honey derived from fynbos, citrus, coriander, and buchu floral sources demonstrated the best anti‐ H. pylori activity (MIC of 6.25%). An increase in anti‐ H. pylori activity was observed for up to 82.50% of combinations of honey and Lactobacillus / Lacticaseibacillus species. A positive correlation (R ² = 0.76) between increased anti‐ H. pylori activity and increased H ₂ O ₂ concentrations was observed. These results demonstrate not only the potential of South African honey as anti‐ H. pylori agents, but also the importance of their interactions with the gut microbiome to enhance inhibition of this ulcer‐causing pathogen.

Molecularly imprinted polymers (MIPs) have emerged as promising materials for selectively targeting biomolecules, including quorum sensing autoinducers that regulate bacterial communication and biofilm formation. In this study, both single-template and dual-template strategies were employed to design and synthesize MIPs capable of capturing autoinducer-2 analogs using (3R,4S)-tetrahydro-3,4-furandiol (T1) or (R/S) 2,2-dimethyl-1,3-dioxolane-4-methanol (T2) as the templates. This approach offers translational potential of a complementary or non-antibiotic strategy to conventional antimicrobial therapies in mitigating biofilm-associated infections. Computational modeling guided the rational selection of functional monomers, predicting favorable interaction energies (ΔE_C up to −135 kcal·mol⁻¹) and optimal hydrogen-bonding patterns to enhance template–polymer affinity. The synthesized MIPs were characterized using spectroscopic and microscopic techniques to confirm imprinting efficiency and structural integrity. The adsorption capacity measurements demonstrated higher adsorption capacity and selectivity of MIPs compared to non-imprinted polymers, with the highest selectivity equal to 3.36 for T1 and 3.14 for T2 on MIPs fabricated from methacrylic acid. Preliminary microbiological evaluations using Chromobacterium violaceum ATCC 12472 reveal that the MIPs prepared from 2-hydroxyethyl methacrylate effectively inhibited violacein production by up to 78.2% at 5.0 mg·mL⁻¹, consistent with quorum sensing interference. These findings highlight the feasibility of employing molecular imprinting to target autoinducer-2 analogs, introducing a novel synthetic strategy for disrupting bacterial communication. This further suggests that molecular imprinting can be leveraged to develop potent quorum-sensing inhibitors, an approach that offers translational potential as an alternative to conventional antimicrobial strategies to mitigate biofilm-associated infections.