Disrupted Iron Metabolism and Mortality during Co-infection with Malaria and an Intestinal Gram-Negative Extracellular Pathogen.
Disrupted Iron Metabolism and Mortality during Co-infection with Malaria and an Intestinal Gram-Negative Extracellular Pathogen.
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DOI：
10.1016/j.celrep.2020.108613
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发表时间：
2021-01-12
期刊：
影响因子：
8.8
通讯作者：
Ribeiro do V Antonelli L
中科院分区：
文献类型：
--
作者：
Dos Santos LI;Torres TA;Diniz SQ;Gonçalves R;Caballero-Flores G;Núñez G;Gazzinelli RT;Maloy KJ;Ribeiro do V Antonelli L
当感染革兰氏阴性（Gr−）细菌时，疟疾患者的发病率和死亡率会增加。为了通过实验探索这一点，我们对小鼠进行了查鲍迪疟原虫和啮齿类柠檬酸杆菌（一种感染大肠的细胞外 Gr− 细菌病原体）的共同感染。虽然单一感染得到有效控制，但合并感染会导致毒力增强，其特点是全身细菌持续时间延长和死亡率高。共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型啮齿类啮齿动物菌株共同感染不会导致死亡。这些结果表明，铁代谢紊乱可能会改变宿主的免疫反应并促进细菌的持久存在，从而在啮齿类柠檬酸杆菌和查鲍迪疟原虫共同感染期间导致死亡率增加。疟疾和革兰氏阴性细菌病原体合并感染导致高死亡率 合并感染导致血浆血红素升高和全身细菌持久性 铁的获取对于细菌持久性和死亡率至关重要 患有疟疾和菌血症的个体的死亡率高于单独感染疟疾的个体。多斯桑托斯等人。报告称，啮齿类柠檬酸杆菌和恰鲍迪疟原虫的共同感染会导致高死亡率，这与血浆血红素增加、细菌持续存在和宿主免疫力改变有关。
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. Co-infection with malaria and a Gram-negative bacterial pathogen leads to high mortality Co-infection leads to elevated plasma heme and systemic bacterial persistence Iron acquisition is critical for bacterial persistence and mortality Mortality of individuals with malaria and bacteremia is higher than with malaria alone. dos Santos et al. report that co-infection with Citrobacter rodentium and Plasmodium chabaudi results in high mortality that is associated with increased plasma heme, sustained bacterial persistence, and altered host immunity.
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影响因子：
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作者：
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通讯作者：
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DOI：
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发表时间：
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影响因子：
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DOI：
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发表时间：
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