Somandi Khonzisizwe, Mwale Tama S, Sobiech Monika, Klejn Dorota, Mahumane Gillian D, Giebułtowicz Joanna, Vuuren Sandy van, Choonara Yahya E, Luliński Piotr
Wits Advanced Drug Delivery Platform Research Unit, 7 York Road, Parktown, Johannesburg 2193, South Africa.
Department of Pharmacy and Pharmacology, School of Therapeutic Science, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown, Johannesburg 2193, South Africa.
Int J Mol Sci. 2025 Aug 19;26(16):8015. doi: 10.3390/ijms26168015.
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 () or (R/S) 2,2-dimethyl-1,3-dioxolane-4-methanol () 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 ( up to -135 kcal·mol) 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 and 3.14 for on MIPs fabricated from methacrylic acid. Preliminary microbiological evaluations using 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, 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.
分子印迹聚合物（MIPs）已成为用于选择性靶向生物分子的有前景的材料，这些生物分子包括调节细菌通讯和生物膜形成的群体感应自诱导物。在本研究中，采用单模板和双模板策略来设计和合成能够使用（3R，4S）-四氢-3,4-呋喃二醇（）或（R/S）2,2-二甲基-1,3-二氧戊环-4-甲醇（）作为模板捕获自诱导物-2类似物的MIPs。这种方法为传统抗菌疗法在减轻生物膜相关感染方面提供了一种补充性或非抗生素策略的转化潜力。计算建模指导了功能单体的合理选择，预测了有利的相互作用能（高达-135 kcal·mol）和最佳氢键模式以增强模板-聚合物亲和力。使用光谱和显微镜技术对合成的MIPs进行表征，以确认印迹效率和结构完整性。吸附容量测量表明，与非印迹聚合物相比，MIPs具有更高的吸附容量和选择性，在由甲基丙烯酸制备的MIPs上，对的最高选择性等于3.36，对的最高选择性等于3.14。使用ATCC 12472进行的初步微生物学评估表明，由甲基丙烯酸羟乙酯制备的MIPs在5.0 mg·mL时可有效抑制紫色杆菌素的产生，高达78.2%，这与群体感应干扰一致。这些发现突出了采用分子印迹靶向自诱导物-2类似物的可行性，引入了一种破坏细菌通讯的新型合成策略。这进一步表明，分子印迹可用于开发有效的群体感应抑制剂，这种方法作为减轻生物膜相关感染的传统抗菌策略的替代方法具有转化潜力。
