Neumann Wilma, Hadley Rose C, Nolan Elizabeth M
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, U.S.A.
Essays Biochem. 2017 May 9;61(2):211-223. doi: 10.1042/EBC20160084.
Transition metals are essential nutrients for all organisms and important players in the host-microbe interaction. During bacterial infection, a tug-of-war between the host and microbe for nutrient metals occurs: the host innate immune system responds to the pathogen by reducing metal availability and the pathogen tries to outmaneuver this response. The outcome of this competition, which involves metal-sequestering host-defense proteins and microbial metal acquisition machinery, is an important determinant for whether infection occurs. One strategy bacterial pathogens employ to overcome metal restriction involves hijacking abundant host metalloproteins. The obligate human pathogens and express TonB-dependent transport systems that capture human metalloproteins, extract the bound metal ions, and deliver these nutrients into the bacterial cell. This review highlights structural and mechanistic investigations that provide insights into how acquire iron from the Fe(III)-transport protein transferrin (TF), the Fe(III)-chelating host-defense protein lactoferrin (LF), and the oxygen-transport protein hemoglobin (Hb), and obtain zinc from the metal-sequestering antimicrobial protein calprotectin (CP).
过渡金属是所有生物体必需的营养素，也是宿主与微生物相互作用中的重要参与者。在细菌感染期间，宿主和微生物之间会为了营养金属展开一场拉锯战：宿主先天免疫系统通过减少金属可利用性来应对病原体，而病原体则试图巧妙应对这种反应。这场竞争的结果，涉及金属螯合宿主防御蛋白和微生物金属获取机制，是感染是否发生的重要决定因素。细菌病原体用来克服金属限制的一种策略是劫持丰富的宿主金属蛋白。专性人类病原体和表达依赖TonB的转运系统，该系统捕获人类金属蛋白，提取结合的金属离子，并将这些营养物质输送到细菌细胞中。本综述重点介绍了结构和机制研究，这些研究为如何从铁（III）转运蛋白转铁蛋白（TF）、铁（III）螯合宿主防御蛋白乳铁蛋白（LF）和氧转运蛋白血红蛋白（Hb）中获取铁，以及从金属螯合抗菌蛋白钙卫蛋白（CP）中获取锌提供了见解。
