Jain Sunny, Showman Adrienne C, Jewett Mollie W
Burnett School of Biomedical Sciences, University of Central Florida College of Medicine, Orlando, Florida, USA.
Burnett School of Biomedical Sciences, University of Central Florida College of Medicine, Orlando, Florida, USA
Infect Immun. 2015 Jun;83(6):2224-33. doi: 10.1128/IAI.02859-14. Epub 2015 Mar 16.
The Lyme disease spirochete Borrelia burgdorferi is dependent on purine salvage from the host environment for survival. The genes bbb22 and bbb23 encode purine permeases that are essential for B. burgdorferi mouse infectivity. We now demonstrate the unique contributions of each of these genes to purine transport and murine infection. The affinities of spirochetes carrying bbb22 alone for hypoxanthine and adenine were similar to those of spirochetes carrying both genes. Spirochetes carrying bbb22 alone were able to achieve wild-type levels of adenine saturation but not hypoxanthine saturation, suggesting that maximal hypoxanthine uptake requires the presence of bbb23. Moreover, the purine transport activity conferred by bbb22 was dependent on an additional distal transcriptional start site located within the bbb23 open reading frame. The initial rates of uptake of hypoxanthine and adenine by spirochetes carrying bbb23 alone were below the level of detection. However, these spirochetes demonstrated a measurable increase in hypoxanthine uptake over a 30-min time course. Our findings indicate that bbb22-dependent adenine transport is essential for B. burgdorferi survival in mice. The bbb23 gene was dispensable for B. burgdorferi mouse infectivity, yet its presence was required along with that of bbb22 for B. burgdorferi to achieve maximal spirochete loads in infected mouse tissues. These data demonstrate that both genes, bbb22 and bbb23, are critical for B. burgdorferi to achieve wild-type infection of mice and that the differences in the capabilities of the two transporters may reflect distinct purine salvage needs that the spirochete encounters throughout its natural infectious cycle.
莱姆病螺旋体伯氏疏螺旋体依赖从宿主环境中获取嘌呤来维持生存。基因bbb22和bbb23编码嘌呤通透酶，这些酶对于伯氏疏螺旋体感染小鼠至关重要。我们现在证明了这两个基因各自对嘌呤转运和小鼠感染的独特贡献。仅携带bbb22的螺旋体对次黄嘌呤和腺嘌呤的亲和力与携带这两个基因的螺旋体相似。仅携带bbb22的螺旋体能够达到野生型腺嘌呤饱和水平，但不能达到次黄嘌呤饱和水平，这表明最大次黄嘌呤摄取需要bbb23的存在。此外，bbb22赋予的嘌呤转运活性依赖于位于bbb23开放阅读框内的一个额外的远端转录起始位点。仅携带bbb23的螺旋体对次黄嘌呤和腺嘌呤的初始摄取速率低于检测水平。然而，这些螺旋体在30分钟的时间进程中显示出次黄嘌呤摄取有可测量的增加。我们的研究结果表明，依赖bbb22的腺嘌呤转运对于伯氏疏螺旋体在小鼠中的生存至关重要。bbb23基因对于伯氏疏螺旋体感染小鼠并非必需，但它与bbb22一起存在时，伯氏疏螺旋体才能在感染的小鼠组织中达到最大螺旋体载量。这些数据表明，bbb22和bbb23这两个基因对于伯氏疏螺旋体实现对小鼠的野生型感染都至关重要，并且这两种转运蛋白能力的差异可能反映了螺旋体在其自然感染周期中遇到的不同嘌呤补救需求。
