Department of Microbiology and Immunology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, Virginia 23298, USA.
Infect Immun. 2011 Jan;79(1):267-78. doi: 10.1128/IAI.00807-10. Epub 2010 Nov 1.
Neisseria gonorrhoeae produces no known siderophores but can employ host-derived, iron-binding proteins, including transferrin and lactoferrin, as iron sources. Given the propensity of this pathogen to hijack rather than synthesize iron-sequestering molecules, we hypothesized that the ability to use siderophores produced by other bacteria, or xenosiderophores, may also play a role in the survival of the gonococcus. Among a panel of diverse siderophores, only the catecholate xenosiderophores enterobactin and salmochelin promoted growth of gonococcal strain FA19. Surprisingly, the internalization pathway was independent of TonB or any of the TonB-dependent transporters. Xenosiderophore-mediated growth was similarly independent of the pilin-extruding secretin formed by PilQ and of the hydrophobic-agent efflux system composed of MtrCDE. The fbpABC operon encodes a periplasmic-binding-protein-dependent ABC transport system that enables the gonococcus to transport iron into the cell subsequent to outer membrane translocation. We hypothesized that the FbpABC proteins, required for ferric iron transport from transferrin and lactoferrin, might also contribute to the utilization of xenosiderophores as iron sources. We created mutants that conditionally expressed FbpABC from an IPTG-inducible promoter. We determined that expression of FbpABC was required for growth of gonococcal strain FA19 in the presence of enterobactin and salmochelin. The monomeric component of enterobactin, dihydroxybenzoylserine (DHBS), and the S2 form of salmochelin specifically promoted FbpABC-dependent growth of FA19. This study demonstrated that the gonococcal FbpABC transport system is required for utilization of some xenosiderophores as iron sources and that growth promotion by these ferric siderophores can occur in the absence of TonB or individual TonB-dependent transporters.
淋病奈瑟菌不产生任何已知的铁载体，但可以利用宿主来源的、与铁结合的蛋白质，包括转铁蛋白和乳铁蛋白，作为铁源。鉴于该病原体倾向于劫持而不是合成铁螯合分子，我们假设利用其他细菌产生的铁载体或异种铁载体的能力也可能在淋球菌的生存中发挥作用。在一组不同的铁载体中，只有儿茶酚型异种铁载体肠杆菌素和沙门氏菌素促进了菌株 FA19 的生长。令人惊讶的是，内化途径不依赖于 TonB 或任何 TonB 依赖性转运体。异种铁载体介导的生长同样独立于由 PilQ 形成的、由 MtrCDE 组成的疏水性药物外排系统的菌毛挤出分泌素。fbpABC 操纵子编码一个周质结合蛋白依赖性 ABC 转运系统，使淋球菌能够在穿过外膜后将铁转运到细胞内。我们假设，FbpABC 蛋白是从转铁蛋白和乳铁蛋白中转运铁所必需的，也可能有助于将异种铁载体用作铁源。我们创建了条件性表达 IPTG 诱导启动子的 FbpABC 突变体。我们确定，FbpABC 的表达对于菌株 FA19 在肠杆菌素和沙门氏菌素存在下的生长是必需的。肠杆菌素的单体成分二羟苯丙氨酸（DHBS）和沙门氏菌素的 S2 形式特异性促进了 FA19 依赖 FbpABC 的生长。这项研究表明，淋球菌的 FbpABC 转运系统是利用一些异种铁载体作为铁源所必需的，并且这些三价铁载体的生长促进作用可以在没有 TonB 或单个 TonB 依赖性转运体的情况下发生。
