Laboratory of Feed Biotechnology, State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China.
College of Bioengineering, Sichuan University of Science & Engineering, Zigong 643000, China.
Int J Mol Sci. 2021 Oct 28;22(21):11681. doi: 10.3390/ijms222111681.
The increasing numbers of infections caused by multidrug-resistant (MDR) pathogens highlight the urgent need for new alternatives to conventional antibiotics. Antimicrobial peptides have the potential to be promising alternatives to antibiotics because of their effective bactericidal activity and highly selective toxicity. The present study was conducted to investigate the antibacterial, antibiofilm, and anti-adhesion activities of different CTP peptides (CTP: the original hybrid peptide cathelicidin 2 (1-13)-thymopentin (TP5); CTP-NH: C-terminal amidated derivative of cathelicidin 2 (1-13)-TP5; CTPQ: glutamine added at the C-terminus of cathelicidin 2 (1-13)-TP5) by determining the minimal inhibitory concentrations (MICs), minimal bactericidal concentrations (MBCs), propidium iodide uptake, and analysis by scanning electron microscopy, transmission electron microscopy, and confocal laser scanning microscopy). The results showed that CTPs had broad-spectrum antibacterial activity against different gram-positive and gram-negative bacteria, with MICs against the tested strains varying from 2 to 64 μg/mL. CTPs at the MBC (2 × MIC 64 μg/mL) showed strong bactericidal effects on a standard methicillin-resistant strain ATCC 43300 after co-incubation for 6 h through disruption of the bacterial membrane. In addition, CTPs at 2 × MIC also displayed effective inhibition activity of several strains with a 40-90% decrease in biofilm formation by killing the bacteria embedded in the biofilms. CTPs had low cytotoxicity on the intestinal porcine epithelial cell line (IPEC-J2) and could significantly decrease the rate of adhesion of ATCC 43300 on IPEC-J2 cells. The current study proved that CTPs have effective antibacterial, antibiofilm, and anti-adhesion activities. Overall, this study contributes to our understanding of the possible antibacterial and antibiofilm mechanisms of CTPs, which might be an effective anti-MDR drug candidate.
越来越多的多药耐药（MDR）病原体感染凸显了急需新型抗生素替代品的迫切需求。抗菌肽因其有效的杀菌活性和高度选择性的毒性而有可能成为抗生素的替代品。本研究旨在通过测定最小抑菌浓度（MIC）、最小杀菌浓度（MBC）、碘化丙啶摄取以及扫描电子显微镜、透射电子显微镜和共聚焦激光扫描显微镜分析，研究不同 CTP 肽（CTP：原始杂合肽抗菌肽 2（1-13）-胸腺五肽（TP5）；CTP-NH：抗菌肽 2（1-13）-TP5 的 C 末端酰胺化衍生物；CTPQ：在抗菌肽 2（1-13）-TP5 的 C 末端添加谷氨酰胺）的抗菌、抗生物膜和抗黏附活性。结果表明，CTP 对不同的革兰氏阳性和革兰氏阴性菌具有广谱抗菌活性，对测试菌株的 MIC 范围为 2 至 64 μg/mL。CTP 在 MBC（2×MIC 64 μg/mL）下，通过破坏细菌膜，在 6 h 共孵育后对标准耐甲氧西林 菌株 ATCC 43300 显示出强大的杀菌作用。此外，在 2×MIC 下，CTP 还对几种菌株表现出有效的抑制活性，通过杀死嵌入生物膜中的细菌，使生物膜形成减少 40-90%。CTP 对肠猪上皮细胞系（IPEC-J2）的细胞毒性低，可显著降低 ATCC 43300 在 IPEC-J2 细胞上的黏附率。本研究证明 CTP 具有有效的抗菌、抗生物膜和抗黏附活性。总的来说，这项研究有助于我们了解 CTP 的可能的抗菌和抗生物膜机制，这可能是一种有效的抗 MDR 药物候选物。
