Arzese Alessandra, Skerlavaj Barbara, Tomasinsig Linda, Gennaro Renato, Zanetti Margherita
Institute of Microbiology, Udine Medical School, University of Udine, p.zza S.M. Misericordia 1, 33100 Udine, Italy.
J Antimicrob Chemother. 2003 Sep;52(3):375-81. doi: 10.1093/jac/dkg372. Epub 2003 Aug 13.
The cathelicidin-derived peptide SMAP-29 exerts rapid and broad-spectrum antimicrobial activity against aerobic bacteria and fungi. In this study, the effects of the peptide against the Bacteroides fragilis group, including antibiotic-resistant isolates, Clostridium perfringens and Clostridium difficile reference and clinical isolates, were investigated.
The microbicidal activity of SMAP-29 against eight reference and 100 clinical anaerobic strains from a national collection was assessed using a microdilution susceptibility assay, and by determining the killing kinetics on selected strains. The killing mechanism was investigated further by means of a two-colour fluorescent permeabilization assay, and by scanning electron microscopy (SEM).
The Bacteroides fragilis group, Clostridium reference strains and most clinical isolates were inhibited in vitro by 1-2 microM (3.2-6.4 mg/L) SMAP-29, and killed by 1.5- to 2-fold higher peptide concentrations. The anaerobic bacterial cells were 90%-100% permeabilized within 2 h of exposure to bactericidal concentrations of the peptide. The SEM images of bacteria exposed to SMAP-29 provide morphological evidence that the envelope is an important target of the bactericidal activity of this peptide. These results are consistent with earlier studies indicating that SMAP-29 kills aerobic bacteria with a membranolytic mechanism, and suggest that both aerobic and anaerobic bacteria share surface features that are targeted by this peptide.
These studies demonstrate that the spectrum of antibacterial activity of SMAP-29 includes the B. fragilis group and Clostridium species, and encourage further investigations of the therapeutic potential of this peptide.
来源于杀菌肽的SMAP-29对需氧菌和真菌具有快速且广谱的抗菌活性。在本研究中，我们调查了该肽对脆弱拟杆菌属（包括耐药菌株）、产气荚膜梭菌以及艰难梭菌参考菌株和临床分离株的作用。
使用微量稀释药敏试验，并通过测定选定菌株的杀菌动力学，评估了SMAP-29对来自国家菌种保藏中心的8株参考菌株和100株临床厌氧菌株的杀菌活性。通过双色荧光通透试验和扫描电子显微镜（SEM）进一步研究了其杀菌机制。
脆弱拟杆菌属、梭菌参考菌株和大多数临床分离株在体外被1-2微摩尔（3.2-6.4毫克/升）的SMAP-29抑制，并在肽浓度高出1.5至2倍时被杀死。厌氧细菌细胞在暴露于杀菌浓度的肽2小时内有90%-100%发生通透。暴露于SMAP-29的细菌的SEM图像提供了形态学证据，表明包膜是该肽杀菌活性的重要靶点。这些结果与早期研究一致，早期研究表明SMAP-29通过膜溶解机制杀死需氧菌，并表明需氧菌和厌氧菌都具有该肽靶向的表面特征。
这些研究表明SMAP-29的抗菌活性谱包括脆弱拟杆菌属和梭菌属，并鼓励对该肽的治疗潜力进行进一步研究。
