Li Lu, Zeng Yang, Tian Minfang, Cao Huijun, Qiu Zhilang, Guo Guo, Shen Feng, Wang Yuping, Peng Jian
Department of Intensive Care Unit/Centre for Clinical Laboratories, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, People's Republic of China.
Key Laboratory of Infectious Immune and Antibody Engineering of Guizhou Province, Cellular Immunotherapy Engineering Research Center of Guizhou Province, School of Biology and Engineering/School of Basic Medical Sciences, Guizhou Medical University, Guiyang, Guizhou, People's Republic of China.
Microbiol Spectr. 2025 Jul;13(7):e0273824. doi: 10.1128/spectrum.02738-24. Epub 2025 May 16.
The rapid increase in carbapenem-resistant (CRKP) infections, along with the cross-resistance of CRKP to other antibiotics, has created an urgent need for novel therapeutic agents. Among the potential options for next-generation antibiotics, antimicrobial peptides (AMPs) show great promise. In this study, we aimed to elucidate the mechanisms underlying the antibacterial activity against CRKP of an antibacterial peptide named Cecropin-4 (Cec4), which we successfully identified previously. Our results demonstrate that Cec4 not only exhibits rapid antibacterial activity but also effectively inhibits and eradicates bacterial biofilm at a low concentration of 8 µg/mL. Additionally, when used in combination with traditional antibiotics, Cec4 enhances their antibacterial effect. Microscopy techniques, including transmission electron microscopy (TEM), confocal laser scanning microscopy, and scanning electron microscopy (SEM), found that Cec4 destroyed bacteria's cell membrane integrity and increased the membrane permeability (flow cytometry instrument technology further characterization of Cec4 against bacteria antibacterial effect). Furthermore, experiments demonstrated that Cec4 binds to bacterial DNA and RNA of CRKP. Moreover, studies using a mouse skin wound model confirmed the efficacy of Cec4, and transcriptomic analysis shed light on the molecular mechanisms underlying its antibacterial activity. Based on our findings, Cec4 appears to be a promising candidate for combating CRKP infections.IMPORTANCEThe rapid increase in carbapenem-resistant (CRKP) infections and the serious cross-resistance to multiple antibiotics make the development of new therapeutic drugs urgent. Antimicrobial peptides (AMPs) have attracted much attention as a potential option for the next generation of antibiotics. Previous studies have identified the antimicrobial peptide Cecropin-4 (Cec4), and this study further explored its antimicrobial mechanism against CRKP. Studies have found that Cec4 shows high antibacterial activity at low concentrations, can inhibit and eradicate bacterial biofilms, and can also enhance the efficacy of traditional antibiotics. Its mechanism of action, such as destroying cell membranes and binding nucleic acid, has been revealed by various techniques, and its effectiveness has been confirmed , providing a promising candidate drug for combating CRKP infection.
耐碳青霉烯类肺炎克雷伯菌（CRKP）感染的迅速增加，以及CRKP对其他抗生素的交叉耐药性，使得对新型治疗药物的需求变得紧迫。在下一代抗生素的潜在选择中，抗菌肽（AMPs）显示出巨大的潜力。在本研究中，我们旨在阐明一种名为天蚕素-4（Cec4）的抗菌肽对CRKP抗菌活性的潜在机制，该抗菌肽是我们之前成功鉴定出来的。我们的结果表明，Cec4不仅具有快速的抗菌活性，而且在8μg/mL的低浓度下就能有效抑制和根除细菌生物膜。此外，当与传统抗生素联合使用时，Cec4能增强它们的抗菌效果。包括透射电子显微镜（TEM）、共聚焦激光扫描显微镜和扫描电子显微镜（SEM）在内的显微镜技术发现，Cec4破坏了细菌的细胞膜完整性并增加了膜通透性（流式细胞仪技术进一步表征了Cec4对细菌的抗菌效果）。此外，实验表明Cec4与CRKP的细菌DNA和RNA结合。而且，使用小鼠皮肤伤口模型的研究证实了Cec4的疗效，转录组分析揭示了其抗菌活性的分子机制。基于我们的研究结果，Cec4似乎是对抗CRKP感染的一个有前景的候选药物。重要性耐碳青霉烯类肺炎克雷伯菌（CRKP）感染的迅速增加以及对多种抗生素的严重交叉耐药性使得开发新的治疗药物变得紧迫。抗菌肽（AMPs）作为下一代抗生素的潜在选择受到了广泛关注。先前的研究已经鉴定出抗菌肽天蚕素-4（Cec4），本研究进一步探索了其对CRKP的抗菌机制。研究发现，Cec4在低浓度下具有高抗菌活性，能够抑制和根除细菌生物膜，还能增强传统抗生素的疗效。通过各种技术揭示了其作用机制，如破坏细胞膜和结合核酸，并且证实了其有效性，为对抗CRKP感染提供了一种有前景的候选药物。
