PDF(Pubmed)
Abstract：
Spirochetes cause Lyme disease, leptospirosis, syphilis, and several other human illnesses. Unlike other bacteria, spirochete flagella are enclosed within the periplasmic space where the filaments distort and push the cell body by the action of the flagellar motors. We previously demonstrated that the oral pathogen Treponema denticola (Td) and Lyme disease pathogen Borreliella burgdorferi (Bb) form covalent lysinoalanine (Lal) cross-links between conserved cysteine and lysine residues of the FlgE protein that composes the flagellar hook. In Td, Lal is unnecessary for hook assembly but is required for motility, presumably due to the stabilizing effect of the cross-link. Herein, we extend these findings to other, representative spirochete species across the phylum. We confirm the presence of Lal cross-linked peptides in recombinant and in vivo-derived samples from Treponema spp., Borreliella spp., Brachyspira spp., and Leptospira spp. As was observed with Td, a mutant strain of Bb unable to form the cross-link has greatly impaired motility. FlgE from Leptospira spp. does not conserve the Lal-forming cysteine residue which is instead substituted by serine. Nevertheless, Leptospira interrogans FlgE also forms Lal, with several different Lal isoforms being detected between Ser-179 and Lys-145, Lys-148, and Lys-166, thereby highlighting species or order-specific differences within the phylum. Our data reveal that the Lal cross-link is a conserved and necessary posttranslational modification across the spirochete phylum and may thus represent an effective target for the development of spirochete-specific antimicrobials.
摘要：
螺旋体引起莱姆病,钩端螺旋体病,梅毒,和其他几种人类疾病。与其他细菌不同，螺旋体鞭毛被封闭在周质空间内，在那里细丝通过鞭毛马达的作用扭曲并推动细胞体。我们先前证明了口腔病原体密螺旋体（Td）和莱姆病病原体伯氏螺旋体（Bb）在构成鞭毛钩的FlgE蛋白的保守半胱氨酸和赖氨酸残基之间形成共价赖氨酸丙氨酸（Lal）交联。在Td,吊钩组件不需要Lal，但运动需要Lal，可能是由于交联的稳定作用。在这里，我们将这些发现扩展到其他，整个门的代表性螺旋体物种。我们确认了来自密螺旋体属的重组和体内衍生样品中Lal交联肽的存在。,伯氏菌属。,短螺旋体。,和钩端螺旋体。正如Td所观察到的，无法形成交联的Bb突变株极大地损害了运动性。FlgE来自钩端螺旋体属。不保留形成Lal的半胱氨酸残基，后者被丝氨酸取代。然而，问号钩端螺旋体FlgE也形成Lal，在Ser-179和Lys-145，Lys-148和Lys-166之间检测到几种不同的Lal同工型，从而突出了门内的物种或订单特异性差异。我们的数据表明，Lal交联是整个螺旋体门的保守且必要的翻译后修饰，因此可能是开发螺旋体特异性抗微生物剂的有效靶标。
