Antimicrobial activity of SMAP-29 against the Bacteroides fragilis group and clostridia
Antimicrobial activity of SMAP-29 against the Bacteroides fragilis group and clostridia
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DOI：
10.1093/jac/dkg372
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发表时间：
2003-09-01
影响因子：
5.2
通讯作者：
Zanetti, M
中科院分区：
文献类型：
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作者：
Arzese, A;Skerlavaj, B;Zanetti, M
目的：导管素衍生肽 SMAP-29 对需氧细菌和真菌发挥快速、广谱的抗菌活性。在本研究中，研究了该肽对脆弱类杆菌群（包括抗生素耐药菌株、产气荚膜梭菌和艰难梭菌参考菌株和临床菌株）的作用。方法：使用微量稀释药敏试验并确定选定菌株的杀灭动力学，评估了 SMAP-29 对来自国家保藏的 8 种参考菌株和 100 种临床厌氧菌株的杀菌活性。通过双色荧光透化测定和扫描电子显微镜 (SEM) 进一步研究了杀伤机制。结果：1-2 muM (3.2-6.4 mg/L) SMAP-29 在体外可抑制脆弱拟杆菌群、梭状芽胞杆菌参考菌株和大多数临床分离株，并可被 1.5 至 2 倍高肽浓度杀死。厌氧细菌细胞在暴露于杀菌浓度的肽后2小时内被透化90%-100%。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目标。这些结果与早期研究一致，表明 SMAP-29 通过膜溶解机制杀死需氧细菌，并表明需氧细菌和厌氧细菌都具有该肽所针对的表面特征。结论：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物种，并鼓励进一步研究该肽的治疗潜力。
Objectives: 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.Methods: 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).Results: The Bacteroides fragilis group, Clostridium reference strains and most clinical isolates were inhibited in vitro by 1-2 muM (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.Conclusions: 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.