Center for Molecular and Translational Human Infectious Diseases Research, Houston Methodist Research Institute, Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, TX 77030, United States.
Department of Microbiology, Cornell University, Ithaca, NY 14853-8101, United States.
EBioMedicine. 2017 Jul;21:131-141. doi: 10.1016/j.ebiom.2017.05.030. Epub 2017 Jun 2.
Bacterial pathogens must overcome host immune mechanisms to acquire micronutrients for successful replication and infection. Streptococcus pyogenes, also known as group A streptococcus (GAS), is a human pathogen that causes a variety of clinical manifestations, and disease prevention is hampered by lack of a human GAS vaccine. Herein, we report that the mammalian host recruits calprotectin (CP) to GAS infection sites and retards bacterial growth by zinc limitation. However, a GAS-encoded zinc importer and a nuanced zinc sensor aid bacterial defense against CP-mediated growth inhibition and contribute to GAS virulence. Immunization of mice with the extracellular component of the zinc importer confers protection against systemic GAS challenge. Together, we identified a key early stage host-GAS interaction and translated that knowledge into a novel vaccine strategy against GAS infection. Furthermore, we provided evidence that a similar struggle for zinc may occur during other streptococcal infections, which raises the possibility of a broad-spectrum prophylactic strategy against multiple streptococcal pathogens.
细菌病原体必须克服宿主的免疫机制，以获取微量元素来成功复制和感染。化脓性链球菌，也称为 A 组链球菌（GAS），是一种人类病原体，可引起多种临床表现，而缺乏人类 GAS 疫苗则阻碍了疾病的预防。在此，我们报告哺乳动物宿主将钙卫蛋白（CP）募集到 GAS 感染部位，并通过锌限制来减缓细菌生长。然而，GAS 编码的锌转运体和精细的锌传感器有助于细菌抵御 CP 介导的生长抑制，并有助于 GAS 毒力。用锌转运体的细胞外成分免疫小鼠可提供针对全身性 GAS 挑战的保护。总之，我们确定了一个关键的早期宿主-GAS 相互作用，并将该知识转化为针对 GAS 感染的新型疫苗策略。此外，我们提供的证据表明，在其他链球菌感染期间可能会发生类似的锌争夺，这增加了针对多种链球菌病原体的广谱预防策略的可能性。
