South Texas Center for Emerging Infectious Diseases and Department of Biology, The University of Texas at San Antonio, San Antonio, TX 78249, USA.
Infect Immun. 2011 Aug;79(8):3407-20. doi: 10.1128/IAI.05234-11. Epub 2011 May 31.
Borrelia burgdorferi, the agent of Lyme disease, undergoes rapid adaptive gene expression in response to signals unique to its arthropod vector or vertebrate hosts. Among the upregulated genes under vertebrate host conditions is one of the five annotated homologs of oligopeptide permease A (OppA5, BBA34). A mutant lacking oppA5 was constructed in an lp25-deficient isolate of B. burgdorferi strain B31, and the minimal regions of infectivity were restored via a shuttle vector pBBE22 with or without an intact copy of bba34. Immunoblot analysis of the bba34 mutant revealed a reduction in the levels of RpoS, BosR, and CsrA(Bb) with a concomitant reduction in the levels of OspC, DbpA, BBK32, and BBA64. There were no changes in the levels of OspA, NapA, P66, and three other OppA orthologs. Quantitative transcriptional analysis correlated with the changes in the protein levels. However, the bba34 mutant displayed comparable infectivities in the C3H/HeN mice and the wild-type strain, despite the reduction in several pathogenesis-related proteins. Supplementation of the growth medium with increased levels of select components, notably sodium acetate and sodium bicarbonate, restored the levels of several proteins in the bba34 mutant to wild-type levels. We speculate that the transport of acetate appears to contribute to the accumulation of key metabolites, like acetyl phosphate, that facilitate the adaptation of B. burgdorferi to the vertebrate host by the activation of the Rrp2-RpoN-RpoS pathway. These studies underscore the importance of solute transport to host-specific adaptation of B. burgdorferi.
伯氏疏螺旋体是莱姆病的病原体，它会针对节肢动物载体或脊椎动物宿主所特有的信号，迅速进行适应性基因表达。在脊椎动物宿主条件下上调的基因中，有一个寡肽透酶 A（OppA5，BBA34）的 5 个注释同源物之一。在 lp25 缺陷型 B. burgdorferi 株 B31 的缺失突变体中构建了一个缺失 oppA5 的突变体，并通过 shuttle 载体 pBBE22 或带有完整 bba34 拷贝的载体恢复了最小感染性区域。对 bba34 突变体的免疫印迹分析表明，RpoS、BosR 和 CsrA（Bb）的水平降低，同时 OspC、DbpA、BBK32 和 BBA64 的水平降低。OspA、NapA、P66 和另外三个 OppA 直系同源物的水平没有变化。定量转录分析与蛋白质水平的变化相关。然而，尽管几种与发病机制相关的蛋白质减少，bba34 突变体在 C3H/HeN 小鼠和野生型菌株中的感染性相当。在生长培养基中补充选定的成分，特别是乙酸钠和碳酸氢钠，可以将 bba34 突变体中的几种蛋白质的水平恢复到野生型水平。我们推测，乙酸盐的运输似乎有助于关键代谢物（如乙酰磷酸）的积累，通过激活 Rrp2-RpoN-RpoS 途径，促进伯氏疏螺旋体适应脊椎动物宿主。这些研究强调了溶质运输对伯氏疏螺旋体宿主特异性适应的重要性。
