Department of Cell Biology and Molecular Genetics, Maryland Pathogen Research Institute, University of Maryland, College Park, College Park, MD, United States.
Front Cell Infect Microbiol. 2018 Mar 14;8:71. doi: 10.3389/fcimb.2018.00071. eCollection 2018.
The transport and metabolism of glucose has been shown to have far reaching consequences in the transcriptional profile of many bacteria. As glucose is most often the preferred carbon source for bacteria, its presence in the environment leads to the repression of many alternate carbohydrate pathways, a condition known as carbon catabolite repression (CCR). Additionally, the expression of many virulence factors is also dependent on the presence of glucose. Despite its importance, little is known about the transport routes of glucose in the human pathogen . Considering that is an important human pathogen responsible for over 500,000 deaths every year, we characterized the routes of glucose transport in an effort to understand its importance in GAS pathogenesis. Using a deletion of glucokinase (Δ) to block utilization of glucose imported by non-PTS pathways, we determined that of the two glucose transport pathways in GAS (PTS and non-PTS), the non-PTS pathway played a more significant role in glucose transport. However, the expression of both pathways is linked by a currently unknown mechanism, as blocking the non-PTS uptake of glucose reduces (EI) expression. Similar to the effects of the deletion of the PTS pathway, lack of the non-PTS pathway also leads to the early activity of Streptolysin S. However, this early activity did not adversely or favorably affect survival of Δ in whole human blood. In a subcutaneous murine infection model, Δ-infected mice showed increased lesion severity at the local site of infection; although, lesion size and dissemination from the site of infection was similar to wild type. Here, we show that glucose transport in GAS is primarily via a non-PTS pathway. The route of glucose transport differentially affects the survival of GAS in whole human blood, as well as the lesion size at the local site of infection in a murine skin infection model.
葡萄糖的转运和代谢已被证明对许多细菌的转录谱产生深远影响。由于葡萄糖通常是细菌的首选碳源，其在环境中的存在导致许多替代碳水化合物途径被抑制，这种情况被称为碳分解代谢物抑制（CCR）。此外，许多毒力因子的表达也依赖于葡萄糖的存在。尽管其重要性，但人们对人类病原体中的葡萄糖转运途径知之甚少。考虑到 是一种重要的人类病原体，每年导致超过 50 万人死亡，我们描述了葡萄糖在 GAS 中的转运途径，以了解其在 GAS 发病机制中的重要性。通过敲除葡萄糖激酶（Δ）来阻断非 PTS 途径导入的葡萄糖利用，我们确定了 GAS 中的两种葡萄糖转运途径（PTS 和非 PTS）中，非 PTS 途径在葡萄糖转运中起更重要的作用。然而，这两种途径的表达是通过一个目前未知的机制联系在一起的，因为阻断非 PTS 摄取葡萄糖会降低 （EI）的表达。与 PTS 途径缺失的影响类似，缺乏非 PTS 途径也会导致链球菌溶血素 S 的早期活性。然而，这种早期活性并没有对 Δ 在全人血中的存活产生不利或有利的影响。在皮下鼠感染模型中，Δ 感染的小鼠在感染部位的局部表现出更严重的病变；尽管，病变大小和从感染部位的扩散与野生型相似。在这里，我们表明 GAS 中的葡萄糖转运主要通过非 PTS 途径进行。葡萄糖转运途径的差异影响 GAS 在全人血中的存活，以及在鼠皮肤感染模型中感染部位的病变大小。
