Programa para el Doctorado en Biotecnología, Facultad de Ciencias Químico-Biológicas de la Universidad Autónoma de Sinaloa, Av. Americas y Blvd, Universitarios, Culiacán, Sinaloa, Mexico.
Biometals. 2010 Jun;23(3):569-78. doi: 10.1007/s10534-010-9306-4. Epub 2010 Mar 2.
Increased prevalence of antibiotic-resistant bacteria has become a major threat to the health sector worldwide due to their virulence, limited therapeutic options and distribution in both hospital and community settings. Discovery and development of new agents to combat antibiotic-resistant bacteria is thus needed. This study therefore aimed to evaluate the ability of bovine lactoferrin (LF), peptides from two antimicrobial domains lactoferricin B (LFcin17-30) and lactoferrampin (LFampin265-284) and a chimeric construct (LFchimera) containing both peptides, as potential bactericidal agents against clinical isolates of antibiotic-resistant Staphylococcus aureus and Escherichia coli. Results in kinetics of growth show that LF chimera and peptides inhibited the growth of both bacterial species. By confocal microscopy and flow cytometry it was observed that LF and FITC-labeled peptides are able to interact with these bacteria and cause membrane permeabilization, as monitored by propidium iodide staining, these effects were decreased by preincubation with lipopolysaccharide in E. coli. By electron microscopy, a clear cellular damage was observed in bacteria after treatments with LFchimera and peptides, suggesting that interaction and membrane disruption are probably involved as a mechanism of action. In conclusion, results show that LFchimera, LF and peptides have potential as bactericidal agents in the antibiotic-resistant strains of S. aureus and E. coli and also the work strongly suggest that LFcin17-30 and LFampin265-284 acts synergistically with antibiotics against multidrug resistant EPEC and MRSA in vitro.
由于抗生素耐药菌的毒力、治疗选择有限以及在医院和社区环境中的分布，它们的出现已成为全球卫生部门的主要威胁。因此，需要发现和开发新的药物来对抗抗生素耐药菌。本研究旨在评估牛乳铁蛋白（LF）、两种抗菌肽乳铁蛋白肽 B（LFcin17-30）和乳铁蛋白肽（LFampin265-284）以及包含这两种肽的嵌合构建体（LFchimera）作为潜在的杀菌剂，对抗临床分离的抗生素耐药金黄色葡萄球菌和大肠杆菌。生长动力学研究结果表明，LF 嵌合体和肽抑制了两种细菌的生长。通过共聚焦显微镜和流式细胞术观察到 LF 和 FITC 标记的肽能够与这些细菌相互作用并导致膜通透性，通过碘化丙啶染色监测到这些效应被 LPS 预先孵育在大肠杆菌中降低。电子显微镜观察到 LFchimera 和肽处理后细菌出现明显的细胞损伤，表明相互作用和膜破坏可能是一种作用机制。综上所述，结果表明 LFchimera、LF 和肽具有作为杀菌剂的潜力，可用于治疗金黄色葡萄球菌和大肠杆菌的抗生素耐药株，并且该研究强烈表明 LFcin17-30 和 LFampin265-284 与抗生素在体外协同作用，对抗多重耐药性 EPEC 和 MRSA。
