Duquesne Sophie, Petit Vanessa, Peduzzi Jean, Rebuffat Sylvie
Chemistry and Biochemistry of Natural Substances, UMR 5154 CNRS-National Museum of Natural History, Department Regulations, Development and Molecular Diversity, Paris, France.
J Mol Microbiol Biotechnol. 2007;13(4):200-9. doi: 10.1159/000104748.
Microcins are a peculiar class of gene-encoded low-molecular-mass antibacterial peptides secreted by enterobacteria. They contribute to the regulation of microbial competitions within the intestinal microbiota. The genetic systems involved in microcin biosynthesis share a conserved organization. Similar to bacteriocins of Gram-positive bacteria, microcins exert potent antibacterial activity directed against phylogenetically-related bacterial strains, with minimal inhibitory concentrations in the nanomolar range. In contrast to bacteriocins, they display a great structural diversity among the few representatives well characterized until now, that makes difficult the description of microcin subclasses. This review focuses on three microcins, MccE492m that carries a C-terminal posttranslational modification containing a catechol-type siderophore, MccJ25, a cyclic peptide with a unique 'lasso-type' structure and MccC7 or C51, with a common N-formylated heptapeptide-nucleotide structure. We show these microcins exhibit 'Trojan horse' mechanisms of antibacterial activity: either (i) the microcin structure is a mime of an essential element, permitting its recognition by outer membrane receptors used for vital functions in bacteria and further translocation into the periplasmic space, or (ii) it is secreted as a harmless molecule and further processed in susceptible bacteria to form the toxic entity. When inside target bacteria, microcins bind essential enzymes or interact with the inner membrane to form a bacterial killing structure.
微菌素是一类由肠道细菌分泌的特殊的基因编码低分子量抗菌肽。它们有助于调节肠道微生物群内的微生物竞争。参与微菌素生物合成的遗传系统具有保守的组织形式。与革兰氏阳性菌的细菌素类似，微菌素对系统发育相关的细菌菌株具有强大的抗菌活性，最低抑菌浓度在纳摩尔范围内。与细菌素不同的是，在目前已充分表征的少数代表中，它们表现出极大的结构多样性，这使得微菌素亚类的描述变得困难。本综述重点关注三种微菌素：携带含有儿茶酚型铁载体的C末端翻译后修饰的MccE492m、具有独特“套索型”结构的环肽MccJ25以及具有共同的N-甲酰化七肽-核苷酸结构的MccC7或C51。我们发现这些微菌素表现出“特洛伊木马”式的抗菌活性机制：要么（i）微菌素结构模仿一种必需元素，使其能够被用于细菌重要功能的外膜受体识别，并进一步转运到周质空间，要么（ii）它作为一种无害分子分泌，然后在易感细菌中进一步加工形成有毒实体。当进入靶细菌内部时，微菌素会结合必需酶或与内膜相互作用形成细菌杀伤结构。
