Instituto René Rachou, Fundação Oswaldo Cruz, Belo Horizonte 30190-009, Minas Gerais, Brazil; Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.
Instituto René Rachou, Fundação Oswaldo Cruz, Belo Horizonte 30190-009, Minas Gerais, Brazil; Instituto de Ciências Biológicas, Departamento de Bioquimica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Minas Gerais, Brazil.
Cell Rep. 2021 Jan 12;34(2):108613. doi: 10.1016/j.celrep.2020.108613.
Individuals with malaria exhibit increased morbidity and mortality when infected with Gram-negative (Gr-) bacteria. To explore this experimentally, we performed co-infection of mice with Plasmodium chabaudi and Citrobacter rodentium, an extracellular Gr- bacterial pathogen that infects the large intestine. While single infections are controlled effectively, co-infection results in enhanced virulence that is characterized by prolonged systemic bacterial persistence and high mortality. Mortality in co-infected mice is associated with disrupted iron metabolism, elevated levels of plasma heme, and increased mitochondrial reactive oxygen species (ROS) production by phagocytes. In addition, iron acquisition by the bacterium plays a key role in pathogenesis because co-infection with a mutant C. rodentium strain lacking a critical iron acquisition pathway does not cause mortality. These results indicate that disrupted iron metabolism may drive mortality during co-infection with C. rodentium and P. chabaudi by both altering host immune responses and facilitating bacterial persistence.
疟原虫感染者感染革兰氏阴性（Gr-）细菌后发病率和死亡率会增加。为了对此进行实验探索，我们对感染伯氏疟原虫（Plasmodium chabaudi）的小鼠进行了柠檬酸杆菌（Citrobacter rodentium）的混合感染，柠檬酸杆菌是一种感染大肠的胞外 Gr-细菌病原体。虽然单一感染可以得到有效控制，但混合感染会导致毒力增强，其特征是系统性细菌持续存在时间延长和死亡率升高。混合感染小鼠的死亡率与铁代谢紊乱、血浆血红素水平升高以及吞噬细胞线粒体活性氧（ROS）产生增加有关。此外，细菌对铁的获取在发病机制中起着关键作用，因为与缺乏关键铁获取途径的突变柠檬酸杆菌菌株的混合感染不会导致死亡。这些结果表明，铁代谢紊乱可能通过改变宿主免疫反应和促进细菌持续存在，从而导致柠檬酸杆菌和伯氏疟原虫混合感染时的死亡率。
