Tomasinsig Linda, Benincasa Monica, Scocchi Marco, Skerlavaj Barbara, Tossi Alessandro, Zanetti Margherita, Gennaro Renato
Department of Biomedical Science and Biotechnology, University of Udine, Udine, Italy.
Department of Life Sciences, University of Trieste, Trieste, Italy.
Probiotics Antimicrob Proteins. 2010 Mar;2(1):12-20. doi: 10.1007/s12602-010-9035-6.
The in vitro antimicrobial activities and biological effects on host cells were compared for the bovine cathelicidins BMAP-28, an alpha-helical AMP, and Bac5 and Bac7, proline-rich AMPs. Our results confirm that the broad-spectrum activity of BMAP-28 correlates with a high capacity to interact with and permeabilize bacterial membranes, whereas the proline-rich AMPs selectively internalize into the cytoplasm of susceptible Gram-negative bacteria with a non-lytic mechanism. All peptides efficiently translocated into mammalian fibroblastic cells, but while Bac5 and Bac7(1-35) localized to nuclear structures and induced cellular proliferation, BMAP-28 associated with mitochondria and did not induce proliferation. Moreover, BMAP-28 was considerably more cytotoxic than the proline-rich peptides due to cytolytic and pro-apoptotic effects. Our results highlight important functional differences among the bovine cathelicidins and suggest that they contribute to an integrated response of the host to infection, with distinct but complementary activities.
对牛源cathelicidin抗菌肽BMAP-28（一种α-螺旋抗菌肽）以及富含脯氨酸的抗菌肽Bac5和Bac7的体外抗菌活性和对宿主细胞的生物学效应进行了比较。我们的结果证实，BMAP-28的广谱活性与其与细菌膜相互作用并使其通透的高能力相关，而富含脯氨酸的抗菌肽则通过非裂解机制选择性地内化到易感革兰氏阴性菌的细胞质中。所有肽都能有效地转运到哺乳动物成纤维细胞中，但Bac5和Bac7(1-35)定位于核结构并诱导细胞增殖，而BMAP-28与线粒体相关且不诱导增殖。此外，由于细胞溶解和促凋亡作用，BMAP-28的细胞毒性比富含脯氨酸的肽大得多。我们的结果突出了牛源cathelicidin抗菌肽之间重要的功能差异，并表明它们有助于宿主对感染的综合反应，具有不同但互补的活性。
