Borrelia burgdorferi requires glycerol for maximum fitness during the tick phase of the enzootic cycle.
Borrelia burgdorferi requires glycerol for maximum fitness during the tick phase of the enzootic cycle.
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DOI：
10.1371/journal.ppat.1002102
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发表时间：
2011-07
期刊：
影响因子：
6.7
通讯作者：
Schwartz I
中科院分区：
文献类型：
--
作者：
Pappas CJ;Iyer R;Petzke MM;Caimano MJ;Radolf JD;Schwartz I
伯氏疏螺旋体（Borrelia burgdorferi）是莱姆病的螺旋体病原体，是一种媒介传播的病原体，在哺乳动物宿主和蜱虫媒介之间循环。这种复杂的生命周期要求螺旋体调节其基因表达程序，以促进在这些不同环境中的生长和维持。伯氏疏螺旋体含有一个操纵子，据预测该操纵子编码的蛋白质可介导甘油的摄取以及将甘油转化为磷酸二羟丙酮。先前的研究表明，该操纵子在23°C时表达升高，并且在存在替代的西格玛因子RpoS时受到抑制，这表明甘油利用可能在蜱虫阶段发挥重要作用。在当前的研究中，通过对glpD（一个据预测编码甘油 - 3 - 磷酸脱氢酶的基因）进行表达分析和诱变，进一步探索了这种可能性。与在蜱虫中的水平相比，glpD的转录水平在小鼠关节中显著较低。在植入大鼠腹腔的透析膜室中螺旋体生长期间，GlpD蛋白的表达以依赖RpoS的方式受到抑制。在以甘油作为主要碳水化合物补充的培养基中，在25°C体外生长时，野生型伯氏疏螺旋体生长到比glpD突变型螺旋体显著更高的细胞密度。通过针头或蜱虫接种，glpD突变型螺旋体在小鼠中具有完全的感染性。相比之下，在若蜱中，glpD突变体生长到比野生型伯氏疏螺旋体显著更低的密度，并且在若蜱吸血时表现出复制缺陷。这些发现表明，伯氏疏螺旋体在从哺乳动物到蜱虫的转变过程中发生碳水化合物利用的转换。此外，结果表明在感染周期的蜱虫阶段将甘油作为糖酵解的碳水化合物来源的能力对于伯氏疏螺旋体的最佳适应性至关重要。
伯氏疏螺旋体是引起莱姆病的媒介传播病原体。它具有复杂的生命周期，涉及在蜱虫媒介和哺乳动物宿主中生长——这两种不同的环境为伯氏疏螺旋体提供了不同的碳水化合物来源以支持生长。先前的研究表明甘油可能是蜱虫媒介中的一种重要营养物质。在这里我们表明，预测参与甘油代谢的基因在所有蜱虫阶段的表达都显著升高。在哺乳动物宿主中表达的抑制依赖于替代的西格玛因子RpoS。一个不能将甘油转化为磷酸二羟丙酮以支持糖酵解的突变体能够感染小鼠。相比之下，该突变体在若蜱中的水平显著较低，其在若蜱吸血期间复制延迟，并且从若蜱到小鼠的传播需要更长的吸血时间。结果表明在感染周期的蜱虫阶段将甘油作为糖酵解的碳水化合物来源的能力对于伯氏疏螺旋体的最佳适应性至关重要。
Borrelia burgdorferi, the spirochetal agent of Lyme disease, is a vector-borne pathogen that cycles between a mammalian host and tick vector. This complex life cycle requires that the spirochete modulate its gene expression program to facilitate growth and maintenance in these diverse milieus. B. burgdorferi contains an operon that is predicted to encode proteins that would mediate the uptake and conversion of glycerol to dihydroxyacetone phosphate. Previous studies indicated that expression of the operon is elevated at 23°C and is repressed in the presence of the alternative sigma factor RpoS, suggesting that glycerol utilization may play an important role during the tick phase. This possibility was further explored in the current study by expression analysis and mutagenesis of glpD, a gene predicted to encode glycerol 3-phosphate dehydrogenase. Transcript levels for glpD were significantly lower in mouse joints relative to their levels in ticks. Expression of GlpD protein was repressed in an RpoS-dependent manner during growth of spirochetes within dialysis membrane chambers implanted in rat peritoneal cavities. In medium supplemented with glycerol as the principal carbohydrate, wild-type B. burgdorferi grew to a significantly higher cell density than glpD mutant spirochetes during growth in vitro at 25°C. glpD mutant spirochetes were fully infectious in mice by either needle or tick inoculation. In contrast, glpD mutants grew to significantly lower densities than wild-type B. burgdorferi in nymphal ticks and displayed a replication defect in feeding nymphs. The findings suggest that B. burgdorferi undergoes a switch in carbohydrate utilization during the mammal to tick transition. Further, the results demonstrate that the ability to utilize glycerol as a carbohydrate source for glycolysis during the tick phase of the infectious cycle is critical for maximal B. burgdorferi fitness. Borrelia burgdorferi is the vector-borne pathogen that causes Lyme disease. It has a complex life cycle that involves growth in a tick vector and a mammalian host — two diverse environments that present B. burgdorferi with alternative carbohydrate sources for support of growth. Previous studies suggested that glycerol may be an important nutrient in the tick vector. Here we show that genes predicted to be involved in glycerol metabolism have significantly elevated expression during all tick stages. Repression of expression in the mammalian host is dependent on the alternative sigma factor, RpoS. A mutant that cannot convert glycerol into dihydroxyacetone phosphate to support glycolysis was able to infect mice. In contrast, the mutant was present at significantly lower levels in nymphal ticks, its replication was delayed during nymphal feeding and longer feeding times were required for transmission from nymph to mouse. The results demonstrate that the ability to utilize glycerol as a carbohydrate source for glycolysis during the tick phase of the infectious cycle is critical for maximal B. burgdorferi fitness.
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影响因子：
1.3
作者：
Basso, W;Venturini, L;Dubey, JP
通讯作者：
Dubey, JP
影响因子：
3.1
作者：
Bykowski, Tomasz;Woodman, Michael E.;Stevenson, Brian
通讯作者：
Stevenson, Brian
影响因子：
3.2
作者：
Caimano, MJ;Eggers, CH;Radolf, JD
通讯作者：
Radolf, JD
DOI：
10.1073/pnas.0408536102
发表时间：
2005-04-05
影响因子：
11.1
作者：
Fisher, MA;Grimm, D;Gherardini, FC
通讯作者：
Gherardini, FC
影响因子：
3.6
作者：
Hyde JA;Shaw DK;Smith Iii R;Trzeciakowski JP;Skare JT
通讯作者：
Skare JT