Bacillus anthracis Overcomes an Amino Acid Auxotrophy by Cleaving Host Serum Proteins.
Bacillus anthracis Overcomes an Amino Acid Auxotrophy by Cleaving Host Serum Proteins.
复制标题
炭疽芽孢杆菌通过裂解宿主血清蛋白来克服氨基酸营养缺陷型。
DOI：
10.1128/jb.00073-15
复制
发表时间：
2015
影响因子：
3.2
通讯作者：
Maresso,Anthony
中科院分区：
文献类型：
--
作者：
Terwilliger,Austen;Swick,MichelleC;Pflughoeft,KathrynJ;Pomerantsev,Andrei;Lyons,CRick;Koehler,TheresaM;Maresso,Anthony
细菌通过从宿主那里获取营养来支持复制来维持感染。宿主将这些营养物质隔离作为一种限制生长的策略，这一概念被称为“营养免疫”。从历史上看，营养免疫的研究主要集中在铁摄取上，因为许多细菌以血红蛋白（一种丰富的循环蛋白）作为铁的来源。细菌从宿主来源获取其他营养物质（包括氨基酸）的机制尚未得到解决。我们采用了一种新的培养基来模拟人类血清的化学成分，我们在这里展示了炭疽芽孢杆菌，炭疽病的病原体，蛋白质水解人类血红蛋白，释放必需氨基酸，促进其生长。这种特性可以追溯到InhA1（一种分泌的金属蛋白酶）的作用，并延伸到至少三种其他血清蛋白，包括血清白蛋白。结果表明，我们还必须考虑关键宿主蛋白的蛋白质水解是细菌病原体获得必需营养物质的一种方式，我们提供了一个实验框架来确定参与这一过程的宿主和细菌因素。细菌病原体在感染过程中获取营养的机制尚不清楚。在这里，我们使用了一种新的定义培养基，接近人类血清的化学成分，血清模拟（BSM），以更好地模拟细菌血症期间病原体遇到的营养环境。从BSM中去除必需氨基酸，发现血液中血红蛋白和血清白蛋白中含量最多的两种蛋白质可以满足炭疽杆菌（炭疽的病原体）对氨基酸的需求。我们进一步证明血红蛋白被分泌的蛋白酶InhA1蛋白化。这些研究强调，普通的血液蛋白可以成为细菌的营养来源。他们还挑战了血红蛋白仅仅是细菌病原体铁源的历史观点。
Bacteria sustain an infection by acquiring nutrients from the host to support replication. The host sequesters these nutrients as a growth-restricting strategy, a concept termed “nutritional immunity.” Historically, the study of nutritional immunity has centered on iron uptake because many bacteria target hemoglobin, an abundant circulating protein, as an iron source. Left unresolved are the mechanisms that bacteria use to attain other nutrients from host sources, including amino acids. We employed a novel medium designed to mimic the chemical composition of human serum, and we show here that Bacillus anthracis, the causative agent of anthrax disease, proteolyzes human hemoglobin to liberate essential amino acids which enhance its growth. This property can be traced to the actions of InhA1, a secreted metalloprotease, and extends to at least three other serum proteins, including serum albumin. The results suggest that we must also consider proteolysis of key host proteins to be a way for bacterial pathogens to attain essential nutrients, and we provide an experimental framework to determine the host and bacterial factors involved in this process.IMPORTANCEThe mechanisms by which bacterial pathogens acquire nutrients during infection are poorly understood. Here we used a novel defined medium that approximates the chemical composition of human blood serum, blood serum mimic (BSM), to better model the nutritional environment that pathogens encounter during bacteremia. Removing essential amino acids from BSM revealed that two of the most abundant proteins in blood—hemoglobin and serum albumin—can satiate the amino acid requirement for Bacillus anthracis, the causative agent of anthrax. We further demonstrate that hemoglobin is proteolyzed by the secreted protease InhA1. These studies highlight that common blood proteins can be a nutrient source for bacteria. They also challenge the historical view that hemoglobin is solely an iron source for bacterial pathogens.