Regulation of iron metabolism in different bacterial infections
Autor(a) principal: | |
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Data de Publicação: | 2015 |
Tipo de documento: | Dissertação |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10773/14598 |
Resumo: | Iron is found in almost all living organisms, playing a central role in host-pathogen interactions and being crucial for both host and pathogens. In the host, iron is a crucial element, since it plays a key role in biological processes such as oxygen transport, biosynthesis of DNA, energy production and regulation of gene expression. However, high concentrations of iron can also be toxic to cells due to the ability to generate hydroxyl radicals. Thus, vertebrates developed proteins to transport and store iron: transferrin and ferritin, respectivetly. Hepcidin is a key protein of iron metabolism, since it binds to ferroportin, the iron exporter, regulating the release of iron to the serum. On the other hand, iron is also fundamental for pathogens that required it to its growth and proliferation, to the expression of virulence factors and to metabolic processes. Thereby, during infection, the host and the pathogen compete by this metal. Pathogens developed multiple strategies to acquire iron from the host during infection. Thus, making iron unavailable for microorganisms is a central mechanism in host defense. In this work, we investigated the regulation of iron metabolism in host during infection with Listeria monocytogenes, a gram-positive bacterium and Salmonella Typhimurium, a gram-negative bacterium in order to verify whether there are alterations in host iron metabolism depending of infection type and if hepcidin have a central role in these alterations. C57BL6 male mice were infected with 104 CFU of L. monocytogenes, S. Typhimurium, or an equivalent volume of vehicle and sacrificed at different time points. Bacterial load quantification, non-heme iron determination in liver, evaluation of iron distribution in tissue, histopathologic analyses and the expression of genes related with iron metabolism were analyzed. Our results show that in both infections with L. monocytogenes and S. Typhimurium the host immune system are not able to irradiate the infection and, thus, the bacterial load increases during the experiment. Regarding the hematological and serological parameters, a reduction of red blood cells and hematocrit is observed, as well as, of serum iron levels. The levels of interleukin-6 and hepcidin increase at different time points in each infection. Additionally, non-heme iron concentration increases in liver during infection with both pathogens. Histopathological alterations were also detected during infection with L monocytogenes and S. Typhimurium. Our data suggests that both infections induce alterations in host iron metabolism. However, the infection with S. Typhimurium appears to have earlier and more severe effects in the host than infection with L. monocytogenes. |
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Regulation of iron metabolism in different bacterial infectionsBiomedicinaInfecções por bactériasBactérias patogénicasSistema imunitárioMetabolismo do ferroProteínasIron is found in almost all living organisms, playing a central role in host-pathogen interactions and being crucial for both host and pathogens. In the host, iron is a crucial element, since it plays a key role in biological processes such as oxygen transport, biosynthesis of DNA, energy production and regulation of gene expression. However, high concentrations of iron can also be toxic to cells due to the ability to generate hydroxyl radicals. Thus, vertebrates developed proteins to transport and store iron: transferrin and ferritin, respectivetly. Hepcidin is a key protein of iron metabolism, since it binds to ferroportin, the iron exporter, regulating the release of iron to the serum. On the other hand, iron is also fundamental for pathogens that required it to its growth and proliferation, to the expression of virulence factors and to metabolic processes. Thereby, during infection, the host and the pathogen compete by this metal. Pathogens developed multiple strategies to acquire iron from the host during infection. Thus, making iron unavailable for microorganisms is a central mechanism in host defense. In this work, we investigated the regulation of iron metabolism in host during infection with Listeria monocytogenes, a gram-positive bacterium and Salmonella Typhimurium, a gram-negative bacterium in order to verify whether there are alterations in host iron metabolism depending of infection type and if hepcidin have a central role in these alterations. C57BL6 male mice were infected with 104 CFU of L. monocytogenes, S. Typhimurium, or an equivalent volume of vehicle and sacrificed at different time points. Bacterial load quantification, non-heme iron determination in liver, evaluation of iron distribution in tissue, histopathologic analyses and the expression of genes related with iron metabolism were analyzed. Our results show that in both infections with L. monocytogenes and S. Typhimurium the host immune system are not able to irradiate the infection and, thus, the bacterial load increases during the experiment. Regarding the hematological and serological parameters, a reduction of red blood cells and hematocrit is observed, as well as, of serum iron levels. The levels of interleukin-6 and hepcidin increase at different time points in each infection. Additionally, non-heme iron concentration increases in liver during infection with both pathogens. Histopathological alterations were also detected during infection with L monocytogenes and S. Typhimurium. Our data suggests that both infections induce alterations in host iron metabolism. However, the infection with S. Typhimurium appears to have earlier and more severe effects in the host than infection with L. monocytogenes.O ferro é encontrado em quase todos os seres vivos, desempenhando um papel central nas interacções entre o hospedeiro e o patógeno e sendo essencial para ambos. Para o hospedeiro, o ferro é um elemento crucial, uma vez que desempenha um papel chave em processos biológicos como o transporte de oxigénio, a biossíntese de DNA, produção de energia e regulação da expressão génica. No entanto, elevadas concentrações de ferro também podem ser tóxicas para as células devido à capacidade de gerarem radicais hidroxilo. Assim, os vertebrados possuem proteínas para transportar e armazenar o ferro, a transferrina e a ferritina respetivamente. A hepcidina é uma proteína chave do metabolismo do ferro, uma vez que se liga à ferroportina, o exportador do ferro, regulando a libertação de ferro para o soro. Por outro lado, o ferro é também fundamental para os patógenos, que o requerem para o seu crescimento e proliferação, para a expressão de factores de virulência e para vários processos metabólicos. Assim, durante a infecção, o hospedeiro e o patógeno competem por este metal. Os patógenos desenvolveram múltiplas estratégias para adquirir o ferro a partir do hospedeiro durante a infeção. Deste modo, tornar o ferro indisponível para os microrganismos é um mecanismo central na defesa do hospedeiro. Neste trabalho, investigámos a regulação do metabolismo do ferro no hospedeiro durante a infecção com Listeria monocytogenes, uma bactéria gram-positiva e com Salmonella Typhimurium, uma bactéria gram-negativa, de modo a verificar se existem alterações no metabolismo do ferro do hospedeiro dependendo do tipo de infeção e se a hepcidina tem um papel preponderante nestas alterações. Murganhos machos C57BL6 foram infectados com 104 CFU de L. monocytogenes, S. Typhimurium, ou um volume equivalente de veículo e sacrificados a diferentes tempos experimentais. A quantificação da carga bacteriana, determinação do ferro não hémico no fígado, avaliação da distribuição de ferro no tecido, análise histopatológica e a expressão de genes relacionados com o metabolismo do ferro foram analisados. Os nossos resultados mostram que tanto na infeção com L. monocytogenes como na infeção com S. Typhimurium, o sistema imunitário do hospedeiro não é capaz de irradiar a infeção e, assim, a carga bacteriana aumenta durante a experiência. Em relação aos parâmetros hematológicos e serológicos, é observada a redução da quantidade de eritrócitos e do hematócrito, bem como dos níveis de ferro no soro. Os níveis de interleucina-6 e de hepcidina aumentam em diferentes tempos experimentais em cada infeção. Adicionalmente, a concentração de ferro não hémico aumenta no fígado durante a infeção com ambos os patógenos. Foram também detetadas alterações histopatológicas aquando da infeção com L monocytogenes e S. Typhimurium. Os nossos dados sugerem que ambas as infeções induzem alterações no metabolismo do ferro do hospedeiro. Contudo, a infeção com S. Typhimurium parece ter efeitos mais precoces e mais severos no hospedeiro do que a infeção com L. monocytogenes.Universidade de Aveiro2015-09-02T10:23:50Z2015-01-01T00:00:00Z2015info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/10773/14598TID:201588579engFerreira, Patrícia Daniela Oliveirainfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-02-22T11:26:42Zoai:ria.ua.pt:10773/14598Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T02:50:09.102814Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Regulation of iron metabolism in different bacterial infections |
title |
Regulation of iron metabolism in different bacterial infections |
spellingShingle |
Regulation of iron metabolism in different bacterial infections Ferreira, Patrícia Daniela Oliveira Biomedicina Infecções por bactérias Bactérias patogénicas Sistema imunitário Metabolismo do ferro Proteínas |
title_short |
Regulation of iron metabolism in different bacterial infections |
title_full |
Regulation of iron metabolism in different bacterial infections |
title_fullStr |
Regulation of iron metabolism in different bacterial infections |
title_full_unstemmed |
Regulation of iron metabolism in different bacterial infections |
title_sort |
Regulation of iron metabolism in different bacterial infections |
author |
Ferreira, Patrícia Daniela Oliveira |
author_facet |
Ferreira, Patrícia Daniela Oliveira |
author_role |
author |
dc.contributor.author.fl_str_mv |
Ferreira, Patrícia Daniela Oliveira |
dc.subject.por.fl_str_mv |
Biomedicina Infecções por bactérias Bactérias patogénicas Sistema imunitário Metabolismo do ferro Proteínas |
topic |
Biomedicina Infecções por bactérias Bactérias patogénicas Sistema imunitário Metabolismo do ferro Proteínas |
description |
Iron is found in almost all living organisms, playing a central role in host-pathogen interactions and being crucial for both host and pathogens. In the host, iron is a crucial element, since it plays a key role in biological processes such as oxygen transport, biosynthesis of DNA, energy production and regulation of gene expression. However, high concentrations of iron can also be toxic to cells due to the ability to generate hydroxyl radicals. Thus, vertebrates developed proteins to transport and store iron: transferrin and ferritin, respectivetly. Hepcidin is a key protein of iron metabolism, since it binds to ferroportin, the iron exporter, regulating the release of iron to the serum. On the other hand, iron is also fundamental for pathogens that required it to its growth and proliferation, to the expression of virulence factors and to metabolic processes. Thereby, during infection, the host and the pathogen compete by this metal. Pathogens developed multiple strategies to acquire iron from the host during infection. Thus, making iron unavailable for microorganisms is a central mechanism in host defense. In this work, we investigated the regulation of iron metabolism in host during infection with Listeria monocytogenes, a gram-positive bacterium and Salmonella Typhimurium, a gram-negative bacterium in order to verify whether there are alterations in host iron metabolism depending of infection type and if hepcidin have a central role in these alterations. C57BL6 male mice were infected with 104 CFU of L. monocytogenes, S. Typhimurium, or an equivalent volume of vehicle and sacrificed at different time points. Bacterial load quantification, non-heme iron determination in liver, evaluation of iron distribution in tissue, histopathologic analyses and the expression of genes related with iron metabolism were analyzed. Our results show that in both infections with L. monocytogenes and S. Typhimurium the host immune system are not able to irradiate the infection and, thus, the bacterial load increases during the experiment. Regarding the hematological and serological parameters, a reduction of red blood cells and hematocrit is observed, as well as, of serum iron levels. The levels of interleukin-6 and hepcidin increase at different time points in each infection. Additionally, non-heme iron concentration increases in liver during infection with both pathogens. Histopathological alterations were also detected during infection with L monocytogenes and S. Typhimurium. Our data suggests that both infections induce alterations in host iron metabolism. However, the infection with S. Typhimurium appears to have earlier and more severe effects in the host than infection with L. monocytogenes. |
publishDate |
2015 |
dc.date.none.fl_str_mv |
2015-09-02T10:23:50Z 2015-01-01T00:00:00Z 2015 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
format |
masterThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10773/14598 TID:201588579 |
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http://hdl.handle.net/10773/14598 |
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TID:201588579 |
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eng |
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eng |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
dc.publisher.none.fl_str_mv |
Universidade de Aveiro |
publisher.none.fl_str_mv |
Universidade de Aveiro |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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