South Texas Center for Emerging Infectious Diseases (STCEID), Center of Excellence in Infection Genomics and Department of Biology, The University of Texas at San Antonio, San Antonio, Texas, USA.
South Texas Center for Emerging Infectious Diseases (STCEID), Center of Excellence in Infection Genomics and Department of Biology, The University of Texas at San Antonio, San Antonio, Texas, USA
Infect Immun. 2018 Jun 21;86(7). doi: 10.1128/IAI.00057-18. Print 2018 Jul.
, the agent of Lyme disease (LD), uses host-derived signals to modulate gene expression during the vector and mammalian phases of infection. Microarray analysis of mutants lacking the host aptation egulator (BadR) revealed the downregulation of genes encoding enzymes whose role in the pathophysiology of is unknown. Immunoblot analysis of the mutants confirmed reduced levels of these enzymes, and one of these enzymes, encoded by , shares homology to prokaryotic magnesium chelatase and Lon-type proteases. The BB0086 levels in were higher under conditions mimicking those in fed ticks. Mutants lacking had no apparent growth defect but were incapable of colonizing immunocompetent C3H/HeN or immunodeficient SCID mice. Immunoblot analysis revealed reduced levels of proteins critical for the adaptation of to the mammalian host, such as OspC, DbpA, and BBK32. Both RpoS and BosR, key regulators of gene expression in , were downregulated in the mutants. Therefore, we designated BB0086 the host aptation rotein (BadP). Unlike mutants, the control strains established infection in C3H/HeN mice at 4 days postinfection, indicating an early colonization defect in mutants due to reduced levels of the lipoproteins/regulators critical for initial stages of infection. However, mutants survived within dialysis membrane chambers (DMCs) implanted within the rat peritoneal cavity but, unlike the control strains, did not display complete switching of OspA to OspC, suggesting incomplete adaptation to the mammalian phase of infection. These findings have opened a novel regulatory mechanism which impacts the virulence potential of .
伯氏疏螺旋体（Borrelia burgdorferi）是莱姆病（LD）的病原体，它利用宿主来源的信号在媒介和哺乳动物感染阶段调节基因表达。对缺乏宿主适应调节因子（BadR）的突变体进行微阵列分析，揭示了编码酶的基因下调，这些酶在 的病理生理学中的作用尚不清楚。对 突变体的免疫印迹分析证实了这些酶水平降低，其中一种酶由 编码，与原核镁螯合酶和 Lon 型蛋白酶具有同源性。在模拟喂食蜱的条件下， 中的 BB0086 水平更高。缺乏 的突变体没有明显的 生长缺陷，但无法定植免疫功能正常的 C3H/HeN 或免疫缺陷的 SCID 小鼠。免疫印迹分析显示，适应哺乳动物宿主的关键蛋白如 OspC、DbpA 和 BBK32 的水平降低。 中的 RpoS 和 BosR，基因表达的关键调节剂，在 突变体中下调。因此，我们将 BB0086 命名为 宿主适应蛋白（BadP）。与 突变体不同，对照株在感染后 4 天即在 C3H/HeN 小鼠中建立感染，表明突变体在早期定植缺陷，原因是对感染初始阶段至关重要的脂蛋白/调节剂水平降低。然而， 突变体在植入大鼠腹膜腔的透析膜室（DMC）中存活，但与对照株不同，它们没有完全将 OspA 切换到 OspC，表明对哺乳动物感染阶段的不完全适应。这些发现开辟了一个新的调控机制，影响 的毒力潜力。
