Department of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, USA.
Life Sciences Institute, Department of Medicinal Chemistry, Department of Chemistry, Department of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, USA.
mBio. 2018 Nov 6;9(6):e02079-18. doi: 10.1128/mBio.02079-18.
is a Gram-positive bacillus that under conditions of environmental stress, such as low nutrients, can convert from a vegetative bacillus to a highly durable spore that enables long-term survival. The sporulation process is regulated by a sequential cascade of dedicated transcription factors but requires key nutrients to complete, one of which is iron. Iron acquisition by the iron-scavenging siderophore petrobactin is required for vegetative growth of under iron-depleted conditions and in the host. However, the extent to which petrobactin is involved in spore formation is unknown. This work shows that efficient sporulation of requires petrobactin, that the petrobactin biosynthesis operon ( to ) is induced prior to sporulation, and that the siderophore itself associates with spores. Petrobactin is also required for oxidative stress protection during late-stage growth and for wild-type levels of sporulation in sporulation medium. Sporulation in bovine blood was found to be petrobactin dependent. Collectively, the contributions of petrobactin to sporulation as well as growth imply that petrobactin may be required for transmission via the spore during natural infections, in addition to its key known functions during active anthrax infections. causes the disease anthrax, which is transmitted via its dormant, spore phase. However, conversion from bacillus to spore is a complex, energetically costly process that requires many nutrients, including iron. requires the siderophore petrobactin to scavenge iron from host environments. We show that, in the Sterne strain, petrobactin is required for efficient sporulation, even when ample iron is available. The petrobactin biosynthesis operon is expressed during sporulation, and petrobactin is biosynthesized during growth in high-iron sporulation medium, but instead of being exported, the petrobactin remains intracellular to protect against oxidative stress and improve sporulation. It is also required for full growth and sporulation in blood (bovine), an essential step for anthrax transmission between mammalian hosts.
炭疽杆菌是一种革兰氏阳性杆菌，在营养物质匮乏等环境胁迫条件下，能够由营养体转变为具有高度抗逆性的芽孢，从而实现长期存活。芽孢形成过程受到一系列专门转录因子的顺序级联调控，但需要关键营养物质才能完成，其中之一就是铁。在缺铁条件下和宿主体内，铁剥夺时，铁载体皮特巴辛的铁摄取对于营养体的生长是必需的。然而，皮特巴辛在芽孢形成中所起的作用程度尚不清楚。本研究表明，皮特巴辛对于炭疽杆菌高效的芽孢形成是必需的，皮特巴辛生物合成操纵子（ pet ）在芽孢形成之前被诱导，并且该铁载体与芽孢本身结合。皮特巴辛对于晚期生长过程中的氧化应激保护和在芽孢形成培养基中野生型水平的芽孢形成也是必需的。在牛血液中的芽孢形成被发现依赖于皮特巴辛。总之，皮特巴辛对于芽孢形成以及生长的贡献表明，皮特巴辛可能是炭疽杆菌在自然感染过程中通过芽孢传播所必需的，除了其在活性炭疽感染中的关键已知功能之外。炭疽杆菌会引起炭疽病，该病通过其休眠的芽孢阶段传播。然而，由营养体向芽孢的转化是一个复杂的、能量消耗大的过程，需要许多营养物质，包括铁。炭疽杆菌需要铁载体皮特巴辛从宿主环境中摄取铁。我们表明，在斯特恩菌株中，即使有充足的铁，皮特巴辛对于高效的芽孢形成也是必需的。在芽孢形成过程中表达皮特巴辛生物合成操纵子，并且在富含铁的芽孢形成培养基中生长时合成皮特巴辛，但该铁载体没有被输出，而是在细胞内保留以防止氧化应激并提高芽孢形成。在血液（牛）中，它对于充分的生长和芽孢形成也是必需的，这是炭疽杆菌在哺乳动物宿主之间传播的一个重要步骤。
