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抗菌肽对胆结石患者病原体的抗菌活性及协同作用

Antibiotic activity and synergistic effect of antimicrobial peptide against pathogens from a patient with gallstones.

作者信息

Park Yoonkyung, Park Soon Nang, Park Seong-Cheol, Park Joon Yong, Park Yong Ha, Hahm Joon Soo, Hahm Kyung-Soo

机构信息

Research Center for Proteineous Materials, Chosun University, 375 Seosuk-Dong, Dong-Ku, Kwangju 501-759, Republic of Korea.

出版信息

Biochem Biophys Res Commun. 2004 Aug 27;321(3):631-7. doi: 10.1016/j.bbrc.2004.07.008.

Abstract

HP (2-20) is a peptide derived from the N-terminus of Helicobacter pylori ribosomal protein L1 that has been shown to have antimicrobial activity against various species of bacteria. When we tested the effects of HP (2-20), we found that this peptide displayed strong activity against pathogens from a patient with gallstones, but it did not have hemolytic activity against human erythrocytes. We also found that HP (2-20) had potent activity against cefazolin sodium-resistant bacterial cell lines, and that HP (2-20) and cefazolin sodium had synergistic effects against cell lines resistant to the latter. To investigate the mechanism of action of HP (2-20), we performed fluorescence activated flow cytometry using pathogens from the patient with gallstones. As determined by propidium iodide (PI) staining, pathogenic bacteria treated with HP (2-20) showed higher fluorescence intensity than untreated cells, similar to melittin-treated cells, and that HP (2-20) acted in an energy- and salt-dependent manner. Scanning electron microscopy showed that HP (2-20) caused significant morphological alterations in the cell surface of pathogens from the patient with gallstones. By determining their 16S rDNA sequences, we found that both the pathogens from the patient with gallstones and the cefazolin sodium-resistant cell lines showed 100% homology with sequences from Pseudomonas aeruginosa. Taken together, these results suggest that HP (2-20) has antibiotic activity and that it may be used as a lead drug for the treatment of acquired pathogens from patients with gallstones and antibiotic-resistant cell lines.

摘要

HP (2 - 20)是一种源自幽门螺杆菌核糖体蛋白L1 N端的肽,已显示对多种细菌具有抗菌活性。当我们测试HP (2 - 20)的作用时,发现该肽对一名胆结石患者的病原体具有强大活性,但对人红细胞没有溶血活性。我们还发现HP (2 - 20)对头孢唑林钠耐药细菌细胞系具有强效活性,并且HP (2 - 20)与头孢唑林钠对后者的耐药细胞系具有协同作用。为了研究HP (2 - 20)的作用机制,我们使用胆结石患者的病原体进行了荧光激活流式细胞术。通过碘化丙啶(PI)染色测定,用HP (2 - 20)处理的病原菌比未处理的细胞显示出更高的荧光强度,类似于用蜂毒素处理的细胞,并且HP (2 - 20)以能量和盐依赖的方式起作用。扫描电子显微镜显示,HP (2 - 20)使胆结石患者病原体的细胞表面发生了显著的形态改变。通过测定它们的16S rDNA序列,我们发现胆结石患者的病原体和头孢唑林钠耐药细胞系与铜绿假单胞菌的序列均显示出100%的同源性。综上所述,这些结果表明HP (2 - 20)具有抗生素活性,并且它可能用作治疗胆结石患者获得性病原体和抗生素耐药细胞系的先导药物。

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