Normant Vincent, Kuhn Lauriane, Munier Mathilde, Hammann Philippe, Mislin Gaëtan L A, Schalk Isabelle J
CNRS/Université de Strasbourg, UMR7242, ESBS, Bld Sébastien Brant, Illkirch, F-67412 Strasbourg, France.
Plateforme Proteomique Strasbourg - Esplanade, Institut de Biologie Moléculaire et Cellulaire, CNRS, FR1589, 15 rue Descartes, F-67084 Strasbourg Cedex, France.
ACS Infect Dis. 2022 Jan 14;8(1):183-196. doi: 10.1021/acsinfecdis.1c00525. Epub 2021 Dec 8.
Iron is an essential nutriment for almost all organisms, but this metal is poorly bioavailable. During infection, bacteria access iron from the host by importing either iron or heme. , a gram-negative pathogen, secretes two siderophores, pyoverdine (PVD) and pyochelin (PCH), to access iron and is also able to use many siderophores produced by other microorganisms (called xenosiderophores). To access heme, uses three distinct uptake pathways, named Has, Phu, and Hxu. We previously showed that expresses the Has and Phu heme uptake systems and the PVD- and PCH-dependent iron uptake pathways in iron-restricted growth conditions, using proteomic and RT-qPCR approaches. Here, using the same approaches, we show that physiological concentrations of hemin in the bacterial growth medium result in the repression of the expression of the proteins of the PVD- and PCH-dependent iron uptake pathways, leading to less production of these two siderophores. This indicates that the pathogen adapts its phenotype to use hemin as an iron source rather than produce PVD and PCH to access iron. Moreover, the presence of both hemin and a xenosiderophore resulted in (i) the strong induction of the expression of the proteins of the added xenosiderophore uptake pathway, (ii) repression of the PVD- and PCH-dependent iron uptake pathways, and (iii) no effect on the expression levels of the Has, Phu, or Hxu systems, indicating that bacteria use both xenosiderophores and heme to access iron.
铁是几乎所有生物体必需的营养物质，但这种金属的生物利用率很低。在感染过程中，细菌通过摄取铁或血红素来从宿主获取铁。铜绿假单胞菌是一种革兰氏阴性病原体，它分泌两种铁载体，即绿脓菌素（PVD）和绿脓杆菌素（PCH）来获取铁，并且还能够利用其他微生物产生的许多铁载体（称为异源铁载体）。为了摄取血红素，铜绿假单胞菌使用三种不同的摄取途径，分别称为Has、Phu和Hxu。我们之前使用蛋白质组学和RT-qPCR方法表明，在铁限制的生长条件下，铜绿假单胞菌表达Has和Phu血红素摄取系统以及依赖PVD和PCH的铁摄取途径。在这里，使用相同的方法，我们表明细菌生长培养基中生理浓度的血红素会导致依赖PVD和PCH的铁摄取途径的蛋白质表达受到抑制，从而导致这两种铁载体的产生减少。这表明病原体调整其表型以使用血红素作为铁源，而不是产生PVD和PCH来获取铁。此外，血红素和异源铁载体同时存在会导致：（i）添加的异源铁载体摄取途径的蛋白质表达强烈诱导；（ii）依赖PVD和PCH的铁摄取途径受到抑制；（iii）对Has、Phu或Hxu系统的表达水平没有影响，这表明细菌同时使用异源铁载体和血红素来获取铁。
