Two Different Virulence-Related Regulatory Pathways in Borrelia burgdorferi Are Directly Affected by Osmotic Fluxes in the Blood Meal of Feeding Ixodes Ticks.
Two Different Virulence-Related Regulatory Pathways in Borrelia burgdorferi Are Directly Affected by Osmotic Fluxes in the Blood Meal of Feeding Ixodes Ticks.
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DOI：
10.1371/journal.ppat.1005791
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发表时间：
2016-08
期刊：
影响因子：
6.7
通讯作者：
Gherardini FC
中科院分区：
文献类型：
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作者：
Bontemps-Gallo S;Lawrence K;Gherardini FC
莱姆病由伯氏疏螺旋体引起，是一种媒介传播的疾病，要求细菌适应其扁虱媒介和各种哺乳动物宿主中截然不同的环境。扁虱的有效定植(获取阶段)需要细菌适应扁虱的中肠生理。向哺乳动物的成功传播(传播阶段)需要细菌感知并对中肠环境线索做出反应，并在传播到新宿主之前上调关键毒力因子。这里提供的数据表明，似乎影响感染周期两个阶段的一个环境信号是渗透压。虽然在哺乳动物宿主的血液、间质液体和组织中渗透压是恒定的(300mOsm)，但在摄食肩部硬蜱的中肠中渗透压是波动的。从喂食的硬蜱的中肠分离出的血粉的测得渗透压从最初的600mOsm波动到300mOsm的血液样渗透压。摄食后，中肠渗透压回升至600mOsm。值得注意的是，这些变化影响到促进伯氏杆菌获取(HK1-Rrp1)和传播(RRP2-RpoN-rpos)的两个独立调控网络。渗透压的增加影响了野生型菌株的形态和运动能力，并裂解了HK1和Rrp1突变菌株。在低渗透浓度下，疏螺旋体细胞表达哺乳动物感染所需的依赖RpoN-rpos的毒力因子(OspC，DbpA)水平增加。我们的结果强烈表明，渗透压是识别信号的重要组成部分，这些信号允许细菌在伯氏杆菌感染周期的获取和传播阶段调节基因表达。莱姆病病原体伯氏疏螺旋体利用了一种多方面的地方性循环，这种循环需要一种扁虱媒介才能在哺乳动物宿主之间成功传播。两个不同的调控系统控制着完成这一感染循环所需的基因。HK1/Rrp1双组分系统影响哺乳动物和Tick载体之间成功转移所需的基因，而RRP2-RpoN-rpos调节级联调控基因是从Tick传播到新的脊椎动物宿主所必需的。这项研究中提供的数据表明，扁虱中肠渗透压的波动直接影响这两条调节途径。壁虱管腔内的渗透压可根据进入的血液(血粉)的渗透压进行调节，以促进水和离子流入壁虱组织。一个正的水通量对于产生足够的唾液来延长摄食是必不可少的。我们认为，伯氏杆菌利用这一生理参数作为一个重要的信号来适应和调节在硬蜱中生存所需的基因(通过HK1/Rrp1)并传递到新的宿主(通过RRP2-RpoN-rpos)。
Lyme disease, caused by Borrelia burgdorferi, is a vector-borne illness that requires the bacteria to adapt to distinctly different environments in its tick vector and various mammalian hosts. Effective colonization (acquisition phase) of a tick requires the bacteria to adapt to tick midgut physiology. Successful transmission (transmission phase) to a mammal requires the bacteria to sense and respond to the midgut environmental cues and up-regulate key virulence factors before transmission to a new host. Data presented here suggest that one environmental signal that appears to affect both phases of the infective cycle is osmolarity. While constant in the blood, interstitial fluid and tissue of a mammalian host (300 mOsm), osmolarity fluctuates in the midgut of feeding Ixodes scapularis. Measured osmolarity of the blood meal isolated from the midgut of a feeding tick fluctuates from an initial osmolarity of 600 mOsm to blood-like osmolarity of 300 mOsm. After feeding, the midgut osmolarity rebounded to 600 mOsm. Remarkably, these changes affect the two independent regulatory networks that promote acquisition (Hk1-Rrp1) and transmission (Rrp2-RpoN-RpoS) of B. burgdorferi. Increased osmolarity affected morphology and motility of wild-type strains, and lysed Hk1 and Rrp1 mutant strains. At low osmolarity, Borrelia cells express increased levels of RpoN-RpoS-dependent virulence factors (OspC, DbpA) required for the mammalian infection. Our results strongly suggest that osmolarity is an important part of the recognized signals that allow the bacteria to adjust gene expression during the acquisition and transmission phases of the infective cycle of B. burgdorferi. Borrelia burgdorferi, the Lyme disease agent, exploits a multifaceted enzootic cycle that requires a tick vector for successful transmission between mammalian hosts. Two different regulatory systems control genes that are required to complete this infective cycle. The Hk1/Rrp1 two-component system affects genes required for successful transfer between mammal and tick vector while the Rrp2-RpoN-RpoS regulatory cascade modulates genes essential for the transmission from the tick to a new vertebrate host. Data presented in this study indicate that fluctuations in osmolarity in the tick midgut directly affect these two regulatory pathways. Osmolarity in the lumen of the tick adjusts to the osmolarity of the incoming blood (blood meal) to promote water and ion flux into tick tissues. A positive water flux is essential to generate sufficient saliva for prolonged feeding. We propose that B. burgdorferi uses this physiological parameter as an important signal to adapt and regulate genes required for survival in the tick (through Hk1/Rrp1) and transmission to a new host (through Rrp2-RpoN-RpoS).