Zou Zongsen, Robinson John I, Steinberg Lindsey K, Henderson Jeffrey P
Center for Women's Infectious Diseases Research, Washington University School of Medicine, St. Louis, Missouri, USA.
Department of Internal Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, Missouri, USA.
bioRxiv. 2023 Jul 25:2023.07.25.550588. doi: 10.1101/2023.07.25.550588.
Uropathogenic (UPEC) secrete multiple siderophore types to scavenge extracellular iron(III) ions during clinical urinary tract infections, despite the metabolic costs of biosynthesis. Here we find the siderophore enterobactin and its related products to be prominent components of the iron-responsive extracellular metabolome of a model UPEC strain. Using defined enterobactin biosynthesis and import mutants, we identify lower molecular weight, dimeric exometabolites as products of incomplete siderophore catabolism, rather than prematurely released biosynthetic intermediates. In iron acquisition from iron(III)-enterobactin complexes requires intracellular esterases that hydrolyze the siderophore. Although UPEC are equipped to consume the products of completely hydrolyzed enterobactin, we find that enterobactin and its derivatives may be incompletely hydrolyzed to yield products with retained siderophore activity. These results are consistent with catabolic inefficiency as means to obtain more than one iron ion per siderophore molecule. This is compatible with an evolved UPEC strategy to maximize the nutritional returns from metabolic investments in siderophore biosynthesis.
在临床尿路感染期间，尿路致病性大肠杆菌（UPEC）会分泌多种类型的铁载体，以清除细胞外的铁（III）离子，尽管生物合成会消耗代谢成本。在此，我们发现铁载体肠杆菌素及其相关产物是模型UPEC菌株铁响应性细胞外代谢组的主要成分。利用明确的肠杆菌素生物合成和导入突变体，我们确定较低分子量的二聚体胞外代谢物是铁载体不完全分解代谢的产物，而非过早释放的生物合成中间体。从铁（III）-肠杆菌素复合物中获取铁需要细胞内酯酶水解铁载体。尽管UPEC具备消耗完全水解的肠杆菌素产物的能力，但我们发现肠杆菌素及其衍生物可能会不完全水解，从而产生保留铁载体活性的产物。这些结果与分解代谢效率低下这一手段相符，即每个铁载体分子可获得不止一个铁离子。这与UPEC进化出的一种策略相契合，即最大化铁载体生物合成代谢投资的营养回报。
