Disrupted Iron Metabolism and Mortality during Co-infection with Malaria and an Intestinal Gram-Negative Extracellular Pathogen
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Authors
Dos Santos, Luara IsabelaTorres, Thais Abdala
Diniz, Suelen Queiroz.
Goncalves, Ricardo
Caballero-Flores, Gustavo
Nunez, Gabriel
Gazzinelli, Ricardo T
Maloy, Kevin Joseph.
Ribeiro do V Antonelli, Lis
UMass Chan Affiliations
Department of Medicine, Division of Infectious Diseases and ImmunologyDocument Type
Journal ArticlePublication Date
2021-01-12Keywords
Citrobacter rodentiumGram-negative bacteria
Plasmodium
co-infection
heme
hemolysis
iron
malaria
mortality
Bacterial Infections and Mycoses
Immunology of Infectious Disease
Parasitic Diseases
Pathogenic Microbiology
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Show full item recordAbstract
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.Source
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
DOI
10.1016/j.celrep.2020.108613Permanent Link to this Item
http://hdl.handle.net/20.500.14038/41740PubMed ID
33440153Related Resources
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Copyright 2021 The Authors. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0)Distribution License
http://creativecommons.org/licenses/by/4.0/ae974a485f413a2113503eed53cd6c53
10.1016/j.celrep.2020.108613
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Except where otherwise noted, this item's license is described as Copyright 2021 The Authors. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0)