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Bacterial cell wall compounds as promising targets of antimicrobial agents I. Antimicrobial peptides and lipopolyamines

机译：细菌细胞壁化合物作为抗微生物剂I.抗微生物肽和脂聚酰胺的有前景靶标

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The first barrier that an antimicrobial agent must overcome when interacting with its target is the microbial cell wall. In the case of Gram-negative bacteria, additional to the cytoplasmic membrane and the peptidoglycan layer, an outer membrane (OM) is the outermost barrier. The OM has an asymmetric distribution of the lipids with phospholipids and lipopolysaccharide (LPS) located in the inner and outer leaflets, respectively. In contrast, Gram-positive bacteria lack OM and possess a much thicker peptidoglycan layer compared to their Gram-negative counterparts. An additional class of amphiphiles exist in Gram-positives, the lipoteichoic acids (LTA), which may represent important structural components. These long molecules cross-bridge the entire cell envelope with their lipid component inserting into the outer leaflet of the cytoplasmic membrane and the teichoic acid portion penetrating into the peptidoglycan layer. Furthermore, both classes of bacteria have other important amphiphiles, such as lipoproteins, whose importance has become evident only recently.It is not known yet whether any of these amphiphilic components are able to stimulate the immune system under physiological conditions as constituents of intact bacteria. However, all of them have a very high pro-inflammatory activity when released from the cell. Such a release may take place through the interaction with the immune system, or with antibiotics (particularly with those targeting cell wall components), or simply by the bacterial division. Therefore, a given antimicrobial agent must ideally have a double character, namely, it must overcome the bacterial cell wall barrier, without inducing the liberation of the pro-inflammatory amphiphiles. Here, new data are presented which describe the development and use of membrane-active antimicrobial agents, in particular antimicrobial peptides (AMPs) and lipopolyamines. In this way, essential progress was achieved, in particular with respect to the inhibition of deleterious consequences of bacterial infections such as severe sepsis and septic shock.
机译：抗菌剂与其靶标相互作用时必须克服的第一个障碍是微生物细胞壁。对于革兰氏阴性细菌，除了细胞质膜和肽聚糖层外，最外层的屏障是外膜（OM）。 OM具有分别位于内部和外部小叶中的磷脂和脂多糖（LPS）的脂质不对称分布。相反，与革兰氏阴性菌相比，革兰氏阳性菌缺乏OM，肽肽聚糖层厚得多。革兰氏阳性菌中还存在一类两亲物，脂磷壁酸（LTA）可能代表重要的结构成分。这些长分子交叉桥联整个细胞包膜，其脂质成分插入细胞质膜的外部小叶中，而chochochoic acid部分则穿透肽聚糖层。此外，这两类细菌还具有其他重要的两亲性，例如脂蛋白，其重要性直到最近才变得明显。尚不清楚这些两亲性成分中的任何一种是否能够在生理条件下刺激免疫系统作为完整细菌的组成部分。然而，当它们从细胞中释放时，它们都具有非常高的促炎活性。这种释放可以通过与免疫系统或与抗生素（特别是与靶向细胞壁成分的抗生素）的相互作用或仅通过细菌分裂而发生。因此，给定的抗微生物剂在理想情况下必须具有双重特征，即它必须克服细菌细胞壁屏障，而不会诱导促炎性两亲物的释放。在这里，提供了新的数据，这些数据描述了膜活性抗菌剂，特别是抗菌肽（AMPs）和脂多胺的开发和使用。这样，取得了重要的进展，特别是在抑制细菌感染（如严重的败血症和败血性休克）的有害后果方面。

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