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Transferrin-mediated iron sequestration as a novel therapy for bacterial and fungal infections.

ABSTRACT: Pathogenic microbes must acquire essential nutrients, including iron, from the host in order to proliferate and cause infections. Iron sequestration is an ancient host antimicrobial strategy. Thus, enhancing iron sequestration is a promising, novel anti-infective strategy. Unfortunately, small molecule iron chelators have proven difficult to develop as anti-infective treatments, in part due to unacceptable toxicities. Iron sequestration in mammals is predominantly mediated by the transferrin family of iron-binding proteins. In this review, we explore the possibility of administering supraphysiological levels of exogenous transferrin as an iron sequestering therapy for infections, which could overcome some of the problems associated with small molecule chelation. Recent studies suggest that transferrin delivery may represent a promising approach to augment both natural resistance and traditional antibiotic therapy.

SUBMITTER: Bruhn KW

PROVIDER: S-EPMC4659759 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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Transferrin-mediated iron sequestration as a novel therapy for bacterial and fungal infections.

Bruhn Kevin W KW Spellberg Brad B

Current opinion in microbiology 20150809

Pathogenic microbes must acquire essential nutrients, including iron, from the host in order to proliferate and cause infections. Iron sequestration is an ancient host antimicrobial strategy. Thus, enhancing iron sequestration is a promising, novel anti-infective strategy. Unfortunately, small molecule iron chelators have proven difficult to develop as anti-infective treatments, in part due to unacceptable toxicities. Iron sequestration in mammals is predominantly mediated by the transferrin fam ...[more]

PMID: 26261881

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Project description:Nosemosis C, a Nosema disease caused by microsporidia parasite Nosema ceranae, is a significant disease burden of the European honey bee Apis mellifera which is one of the most economically important insect pollinators. Nevertheless, there is no effective treatment currently available for Nosema disease and the disease mechanisms underlying the pathological effects of N. ceranae infection in honey bees are poorly understood. Iron is an essential nutrient for growth and survival of hosts and pathogens alike. The iron tug-of-war between host and pathogen is a central battlefield at the host-pathogen interface which determines the outcome of an infection, however, has not been explored in honey bees. To fill the gap, we conducted a study to investigate the impact of N. ceranae infection on iron homeostasis in honey bees. The expression of transferrin, an iron binding and transporting protein that is one of the key players of iron homeostasis, in response to N. ceranae infection was analysed. Furthermore, the functional roles of transferrin in iron homeostasis and honey bee host immunity were characterized using an RNA interference (RNAi)-based method. The results showed that N. ceranae infection causes iron deficiency and upregulation of the A. mellifera transferrin (AmTsf) mRNA in honey bees, implying that higher expression of AmTsf allows N. ceranae to scavenge more iron from the host for its proliferation and survival. The suppressed expression levels of AmTsf via RNAi could lead to reduced N. ceranae transcription activity, alleviated iron loss, enhanced immunity, and improved survival of the infected bees. The intriguing multifunctionality of transferrin illustrated in this study is a significant contribution to the existing body of literature concerning iron homeostasis in insects. The uncovered functional role of transferrin on iron homeostasis, pathogen growth and honey bee's ability to mount immune responses may hold the key for the development of novel strategies to treat or prevent diseases in honey bees.

Dataset Information

Transferrin-mediated iron sequestration as a novel therapy for bacterial and fungal infections.

Publications

Transferrin-mediated iron sequestration as a novel therapy for bacterial and fungal infections.

Similar Datasets

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