Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, Massachusetts; Institute of Environmental Engineering, Department of Civil, Environmental and Geomatic Engineering, ETH Zürich, Zürich, Switzerland; Department of Biological Sciences, University of Southern California, Los Angeles, California.
Institute of Environmental Engineering, Department of Civil, Environmental and Geomatic Engineering, ETH Zürich, Zürich, Switzerland.
Biophys J. 2022 Jun 7;121(11):2046-2059. doi: 10.1016/j.bpj.2022.05.003. Epub 2022 May 6.
To swim up gradients of nutrients, E. coli senses nutrient concentrations within its periplasm. For small nutrient molecules, periplasmic concentrations typically match extracellular concentrations. However, this is not necessarily the case for saccharides, such as maltose, which are transported into the periplasm via a specific porin. Previous observations have shown that, under various conditions, E. coli limits maltoporin abundance so that, for extracellular micromolar concentrations of maltose, there are predicted to be only nanomolar concentrations of free maltose in the periplasm. Thus, in the micromolar regime, the total uptake of maltose from the external environment into the cytoplasm is limited not by the abundance of cytoplasmic transport proteins but by the abundance of maltoporins. Here, we present results from experiments and modeling suggesting that this porin-limited transport enables E. coli to sense micromolar gradients of maltose despite having a high-affinity ABC transport system that is saturated at these micromolar levels. We used microfluidic assays to study chemotaxis of E. coli in various gradients of maltose and methyl-aspartate and leveraged our experimental observations to develop a mechanistic transport-and-sensing chemotaxis model. Incorporating this model into agent-based simulations, we discover a trade-off between uptake and sensing: although high-affinity transport enables higher uptake rates at low nutrient concentrations, it severely limits the range of dynamic sensing. We thus propose that E. coli may limit periplasmic uptake to increase its chemotactic sensitivity, enabling it to use maltose as an environmental cue.
为了在营养物质浓度梯度上向上游动，大肠杆菌在其周质空间中感知营养物质浓度。对于小分子营养物质，周质空间中的浓度通常与细胞外浓度相匹配。然而，对于像麦芽糖这样的糖类来说，情况并非如此，因为它们是通过特定的孔蛋白运输到周质空间的。先前的观察结果表明，在各种条件下，大肠杆菌限制麦芽糖孔蛋白的丰度，以至于对于细胞外微摩尔浓度的麦芽糖，预测周质空间中游离麦芽糖的浓度只有纳米摩尔。因此，在微摩尔范围内，从外部环境中摄取麦芽糖进入细胞质的总量不是由细胞质转运蛋白的丰度决定，而是由麦芽糖孔蛋白的丰度决定。在这里，我们提出了实验和建模的结果，表明这种孔蛋白限制的运输使大肠杆菌能够感知麦芽糖的微摩尔梯度，尽管它具有高亲和力的 ABC 转运系统在这些微摩尔水平上已经饱和。我们使用微流控测定法研究了大肠杆菌在各种麦芽糖和甲基天冬氨酸梯度中的趋化性，并利用我们的实验观察结果开发了一种机械转运和感应趋化性模型。将该模型纳入基于主体的模拟中，我们发现摄取和感应之间存在权衡：尽管高亲和力的转运可以在低营养浓度下实现更高的摄取率，但它严重限制了动态感应的范围。因此，我们提出大肠杆菌可能会限制周质空间的摄取以增加其趋化敏感性，从而使其能够将麦芽糖用作环境线索。
