A Manganese-independent Aldolase Enables Staphylococcus aureus To Resist Host-imposed Metal Starvation.
A Manganese-independent Aldolase Enables Staphylococcus aureus To Resist Host-imposed Metal Starvation.
复制标题
作者：
金黄色葡萄球菌和许多其他病原体的首选碳源是葡萄糖，其消耗在感染期间至关重要。然而，葡萄糖的利用增加了细胞对锰的需求，锰是一种由宿主隔离的营养素，作为对入侵病原体的防御。因此，细菌必须平衡葡萄糖代谢与金属依赖性过程（如糖酵解）对细胞的需求增加。一个关键的调节器，使S。抵抗金黄色葡萄球菌的营养免疫是ArlRS双组分系统。这项工作揭示了ArlRS调节FdaB的表达，FdaB是一种不依赖金属的果糖1，6-二磷酸醛缩酶。进一步的研究表明，当S。当金黄色葡萄球菌被宿主金属饥饿时，FdaB在功能上取代了金属依赖性同工酶FbaA，从而允许S.金黄色葡萄球菌在培养中抵抗宿主施加的金属饥饿。虽然金属依赖性醛缩酶是典型的锌依赖性，这项工作发现，FbaA需要锰的活动和FdaB保护S。金黄色葡萄球菌从锰饥饿。FbaA和FdaB都对S.金黄色葡萄球菌在野生型小鼠中引起侵袭性疾病。然而，缺乏FdaB的菌株的毒力缺陷在钙卫蛋白缺陷小鼠中被逆转，钙卫蛋白缺陷小鼠在锰螯合中具有缺陷，这表明这种同工酶有助于该病原体在感染期间克服锰限制的能力。累积起来，这些观察结果表明，金属非依赖性醛缩酶FdaB的表达允许S。金黄色葡萄球菌，以减轻增加的需求，锰的葡萄糖消耗强加，并强调了辅因子的灵活性，甚至建立金属酶家族。
The preferred carbon source of Staphylococcus aureus and many other pathogens is glucose, and its consumption is critical during infection. However, glucose utilization increases the cellular demand for manganese, a nutrient sequestered by the host as a defense against invading pathogens. Therefore, bacteria must balance glucose metabolism with the increasing demand that metal-dependent processes, such as glycolysis, impose upon the cell. A critical regulator that enables S. aureus to resist nutritional immunity is the ArlRS two-component system. This work revealed that ArlRS regulates the expression of FdaB, a metal-independent fructose 1,6-bisphosphate aldolase. Further investigation revealed that when S. aureus is metal-starved by the host, FdaB functionally replaces the metal-dependent isozyme FbaA, thereby allowing S. aureus to resist host-imposed metal starvation in culture. Although metal-dependent aldolases are canonically zinc-dependent, this work uncovered that FbaA requires manganese for activity and that FdaB protects S. aureus from manganese starvation. Both FbaA and FdaB contribute to the ability of S. aureus to cause invasive disease in wild-type mice. However, the virulence defect of a strain lacking FdaB was reversed in calprotectin-deficient mice, which have defects in manganese sequestration, indicating that this isozyme contributes to the ability of this pathogen to overcome manganese limitation during infection. Cumulatively, these observations suggest that the expression of the metal-independent aldolase FdaB allows S. aureus to alleviate the increased demand for manganese that glucose consumption imposes, and highlights the cofactor flexibility of even established metalloenzyme families.
登录
查看更多内容
金黄色葡萄球菌全球调节剂MGRA通过控制表面蛋白表达来调节结块和毒力。
影响因子：
6.7
作者：
Crosby HA;Schlievert PM;Merriman JA;King JM;Salgado-Pabón W;Horswill AR
通讯作者：
Horswill AR
影响因子：
15
作者：
Brophy MB;Nakashige TG;Gaillard A;Nolan EM
通讯作者：
Nolan EM
影响因子：
6.7
作者：
Achouiti A;Vogl T;Urban CF;Röhm M;Hommes TJ;van Zoelen MA;Florquin S;Roth J;van 't Veer C;de Vos AF;van der Poll T
通讯作者：
van der Poll T
影响因子：
3
作者：
Andreini, Claudia;Bertini, Ivano;Thornton, Janet M.
通讯作者：
Thornton, Janet M.
DOI：
10.1038/nsb1096-856
发表时间：
1996-10-01
期刊：
NATURE STRUCTURAL BIOLOGY
影响因子：
--
作者：
Blom, NS;Tetreault, S;Sygusch, J
通讯作者：
Sygusch, J