Departamento de Microbiologia, Universidade Federal de Viçosa, Viçosa, Minas Gerais, Brazil
Antimicrob Agents Chemother. 2011 Nov;55(11):5284-93. doi: 10.1128/AAC.00638-11. Epub 2011 Aug 29.
Lantibiotics are antimicrobial peptides produced by Gram-positive bacteria, nisin being the most well-known member. Nisin inhibits peptidoglycan synthesis and forms pores at sensitive membranes upon interaction with lipid II, the essential bacterial cell wall precursor. Bovicin HC5, a bacteriocin produced by Streptococcus bovis HC5, has the putative N-terminal lipid II binding motif, and we investigated the mode of action of bovicin HC5 using both living bacteria and model membranes, with special emphasis on the role of lipid II. Bovicin HC5 showed activity against Staphylococcus cohnii and Staphylococcus warneri, but bovicin HC5 hardly interfered with the membrane potential of S. cohnii. In model membranes, bovicin HC5 was not able to cause carboxyfluorescein release or proton influx from DOPC vesicles containing lipid II. Bovicin HC5 blocked lipid II-dependent pore formation activity of nisin, and a high-affinity interaction with lipid II was observed (apparent binding constant [K(a)] = 3.1 × 10(6) M(-1)), with a 1:1 stoichiometry. In DOPC vesicles containing lipid II, bovicin HC5 was able to assemble with lipid II into a prepore-like structure. Furthermore, we observed pore formation activity of bovicin HC5, which was stimulated by the presence of lipid II, in thin membranes. Moreover, bovicin HC5 induced the segregation of lipid II into domains in giant model membrane vesicles. In conclusion, bovicin HC5 has a primary mode of action similar to that of nisin, but some differences regarding the pore-forming capacity were demonstrated.
类细菌素是革兰氏阳性细菌产生的抗菌肽，其中乳链菌肽最为知名。乳链菌肽通过与脂质 II 相互作用抑制肽聚糖的合成，并在敏感膜上形成孔，脂质 II 是细菌细胞壁前体的必需成分。乳球菌素 HC5 是由乳链球菌 HC5 产生的细菌素，具有假定的 N 端脂质 II 结合基序，我们使用活细菌和模型膜研究了乳球菌素 HC5 的作用模式，特别强调了脂质 II 的作用。乳球菌素 HC5 对凝固酶阴性葡萄球菌和华纳葡萄球菌表现出活性，但乳球菌素 HC5 几乎不干扰凝固酶阴性葡萄球菌的膜电位。在模型膜中，乳球菌素 HC5 不能引起含有脂质 II 的 DOPC 囊泡中的羧基荧光素释放或质子内流。乳球菌素 HC5 阻断了乳链菌肽依赖于脂质 II 的孔形成活性，并观察到与脂质 II 的高亲和力相互作用（表观结合常数 [K(a)] = 3.1×10(6) M(-1)），具有 1:1 的化学计量比。在含有脂质 II 的 DOPC 囊泡中，乳球菌素 HC5 能够与脂质 II 组装成预孔样结构。此外，我们在薄膜中观察到了乳球菌素 HC5 的孔形成活性，这种活性受到脂质 II 的刺激。此外，乳球菌素 HC5 诱导脂质 II 在巨大模型膜泡中形成域。总之，乳球菌素 HC5 的主要作用模式与乳链菌肽相似，但在孔形成能力方面存在一些差异。
