UMMS Affiliation

Department of Medicine, Division of Infectious Diseases and Immunology

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Bacterial Infections and Mycoses | Immunology of Infectious Disease | Parasitic Diseases | Pathogenic Microbiology


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.


Citrobacter rodentium, Gram-negative bacteria, Plasmodium, co-infection, heme, hemolysis, iron, malaria, mortality

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Copyright 2021 The Authors. This is an open access article under the CC BY license (

DOI of Published Version



Dos Santos LI, Torres TA, Diniz SQ, Gonçalves R, Caballero-Flores G, Núñez G, Gazzinelli RT, Maloy KJ, Ribeiro do V Antonelli L. Disrupted Iron Metabolism and Mortality during Co-infection with Malaria and an Intestinal Gram-Negative Extracellular Pathogen. Cell Rep. 2021 Jan 12;34(2):108613. doi: 10.1016/j.celrep.2020.108613. PMID: 33440153. Link to article on publisher's site

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Cell reports

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Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.