Cell-Wall Interactions and the Selective Bacteriostatic Activity of a Miniature Oligo-Acyl-Lysyl
Cell-Wall Interactions and the Selective Bacteriostatic Activity of a Miniature Oligo-Acyl-Lysyl
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DOI：
10.1016/j.bpj.2009.08.006
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发表时间：
2009-10-21
影响因子：
3.4
通讯作者：
Epand, Richard M.
中科院分区：
文献类型：
--
作者：
Epand, Raquel F.;Sarig, Hadar;Epand, Richard M.
寡酰基-赖氨酰，C(12(omega 7))K-beta(12)，仅由三个赖氨酸残基组成。尽管其体积小，但它对革兰氏阳性菌具有强大的抑菌活性，但对革兰氏阴性菌的抑菌活性却低 10 倍。我们跟踪了 C(12(omega 7))K-beta(12) 从最初与细菌表面接触穿过细胞壁一直到细胞质膜的相互作用。与阴离子脂质以及带负电荷的 LPS 和 LTA 的结合具有非常高的亲和力。 C(12(omega 7))K-beta(12) 不能穿过革兰氏阴性菌的外膜；相反，它通过沉积在LPS层上、促进表面粘附并阻止溶质通过来实现其作用。在革兰氏阳性细菌中，含有 LTA 的厚肽聚糖层允许 C(12(omega 7))K-beta(12) 通过并促进其在小周质中的积累。然后，它通过强静电相互作用从该位置被驱动到膜上。尽管该试剂对革兰氏阳性菌具有高效力，但它不能有效地打破细胞质膜的渗透屏障或到达细胞内目标，因为它不与 DNA 相互作用。
The oligo-acyl-lysyl, C(12(omega 7))K-beta(12), is comprised of only three Lys residues. Despite its small size, it exhibits potent bacteriostatic activity against Gram-positive bacteria, but it is similar to 10-fold less potent against Gram-negative bacteria. We followed the interactions Of C(12(omega 7))K-beta(12) from its initial contact with the bacterial surface across the cell wall down to the cytoplasmic membrane. Binding to anionic lipids, as well as to negatively charged LPS and LTA, occurs with very high affinity. The C(12(omega 7))K-beta(12) does not cross the outer membrane of Gram-negative bacteria; rather, it achieves its action by depositing on the LPS layer, promoting surface adhesion and blocking passage of solutes. In Gram-positive bacteria, the thick peptidoglycan layer containing LTA allows passage of C(12(omega 7))K-beta(12) and promotes its accumulation in the small periplasm. From that location it is then driven to the membrane by strong electrostatic interactions. Despite its high potency against Gram-positive bacteria, this agent is not capable of efficiently breaking down the permeability barrier of the cytoplasmic membrane or of reaching an intracellular target, as suggested by the fact that it does not interact with DNA.