Disrupted Iron Metabolism and Mortality during Co-infection with Malaria and an Intestinal Gram-Negative Extracellular Pathogen

Cell Reports

Gabriel Núñez¹  Ricardo Gonçalves¹  Thais Abdala Torres²  Ricardo Tostes Gazzinelli³  Lis Ribeiro do V. Antonelli⁴  Kevin Joseph Maloy⁴  Luara Isabela dos Santos⁵  Gustavo Caballero-Flores⁵  Suelen Queiroz Diniz⁵ 

[1] Instituto de Ciências Biológicas, Departamento de Bioquimica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Minas Gerais, Brazil;Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK;Departamento de Patologia Geral, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, Minhas Gerais, Brazil;Department of Pathology and Rogel Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA;Instituto René Rachou, Fundação Oswaldo Cruz, Belo Horizonte 30190-009, Minas Gerais, Brazil;

关键词: malaria;    Plasmodium;    co-infection;    Gram-negative bacteria;    mortality;    Citrobacter rodentium;   

DOI  :  

来源: DOAJ

【 摘 要 】

Summary: 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.

【 授权许可】

Unknown