Baindara Piyush, Roy Dinata, Mandal Santi M
Animal Sciences Research Center, Division of Animal Sciences, University of Missouri, Columbia, MO 65211, USA.
Department of Zoology, Mizoram University, Aizawl 796004, India.
Bioengineering (Basel). 2024 Aug 21;11(8):855. doi: 10.3390/bioengineering11080855.
Antimicrobial peptides (AMPs) are considered a promising alternative to conventional antibiotics to fight against the rapid evolution of antibiotic resistance. Other than their potent antimicrobial properties, AMP-based vesicles can be used as efficient drug-delivery vehicles. In the present study, we synthesized and characterized a new cyclic AMP, consisting of all-hydrophobic cores with antimicrobial activity against . Interestingly, CycP undergoes supramolecular self-assembly, and self-assembled CycP (sCycP) vesicles are characterized under an electron microscope; however, these vesicles do not display antimicrobial activity. Next, sCycP vesicles are used in combination with SXT (sulfamethoxazole-trimethoprim) vesicles to check the drug loading and delivery capacity of sCycP vesicles to bacterial cell membranes. Interestingly, sCycP vesicles showed synergistic action with SXT vesicles and resulted in a significant reduction in MIC against . Further, electron microscopy confirmed the membrane-specific killing mechanism of SXT-loaded sCycP vesicles. Additionally, CycP showed high binding affinities with the β-lactamase of , which was one of its possible antimicrobial mechanisms of action. Overall, the results suggested that CycP is a novel self-assembled dual-action cyclic AMP with non-cytotoxic properties that can be used alone as an AMP or a self-assembled drug delivery vehicle for antibiotics to combat infections.
抗菌肽（AMPs）被认为是对抗抗生素耐药性快速演变的传统抗生素的一种有前途的替代品。除了其强大的抗菌特性外，基于AMP的囊泡还可作为高效的药物递送载体。在本研究中，我们合成并表征了一种新的环状AMP，其由全疏水核心组成，对……具有抗菌活性。有趣的是，CycP会发生超分子自组装，并且在电子显微镜下对自组装的CycP（sCycP）囊泡进行了表征；然而，这些囊泡不显示抗菌活性。接下来，将sCycP囊泡与SXT（磺胺甲恶唑 - 甲氧苄啶）囊泡联合使用，以检查sCycP囊泡对细菌细胞膜的载药和递送能力。有趣的是，sCycP囊泡与SXT囊泡显示出协同作用，并导致对……的最低抑菌浓度（MIC）显著降低。此外，电子显微镜证实了负载SXT的sCycP囊泡的膜特异性杀伤机制。此外，CycP与……的β - 内酰胺酶表现出高结合亲和力，这是其可能的抗菌作用机制之一。总体而言，结果表明CycP是一种新型的自组装双作用环状AMP，具有无细胞毒性的特性，可单独用作AMP或作为抗生素的自组装药物递送载体来对抗……感染。
