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

Instituto René Rachou. Fundação Oswaldo Cruz. Belo Horizonte, MG, Brazil/ Sir William Dunn School of Pathology. University of Oxford. Oxford, OX1, UK.
Instituto René Rachou. Fundação Oswaldo Cruz. Belo Horizonte, MG, Brazil/Instituto de Ciências Biológicas. Departamento de Bioquimica e Imunologia. Universidade Federal de Minas Gerais. Belo Horizonte, MG, Brazil.
Instituto René Rachou. Fundação Oswaldo Cruz. Belo Horizonte, MG, Brazil/Instituto de Ciências Biológicas. Departamento de Bioquimica e Imunologia. Universidade Federal de Minas Gerais. Belo Horizonte, MG, Brazil.
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, USA.
Department of Pathology and Rogel Cancer Center. University of Michigan Medical School. Ann Arbor, MI, USA.
Instituto René Rachou. Fundação Oswaldo Cruz. Belo Horizonte, MG, Brazil/ Instituto de Ciências Biológicas. Departamento de Bioquimica e Imunologia.Universidade Federal de Minas Gerais. Belo Horizonte, MG, Brazil/University of Massachusetts Medical School. Worcester, MA, USA.
Sir William Dunn School of Pathology. University of Oxford. Oxford, OX1, UK/Institute of Infection, Immunity and Inflammation. University of Glasgow. Glasgow, Scotland.
Instituto René Rachou. Fundação Oswaldo Cruz. Belo Horizonte, MG, Brazil.

Abstract

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

Keywords

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

Publisher

Cell Press

Citation

SANTOS, Luara Isabela dos et al. Disrupted Iron Metabolism and Mortality during Co-infection with Malaria and an Intestinal Gram-Negative Extracellular. Pathogen Cell Rep., v. 34, n. 2, 108613, 2021. doi: 10.1016/j.celrep.2020.108613.

ISSN

2211-1247

Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/51186

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Open access

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