Association of Pulmonary Tuberculosis with Increased Dietary Iron

Gangaidzo, Innocent T.; Moyo, Victor; Mvundura, Elisha; Aggrey, George; Murphree, N. L.; Khumalo, Hlosukwazi; Saungweme, Thokozile; Kasvosve, Ishmael; Gomo, Zvenyika A. R.; Rouault, Tracey A.; Boelaert, Johan R.; Gordeuk, Victor R.

doi:10.1086/323203

Cited by 162 publications

(124 citation statements)

References 13 publications

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“…These findings should also be considered in light of numerous reports that associate high serum iron levels and transferrin-iron saturation with an increased mortality and morbidity due to tuberculosis [16][17][18][19][20] . It is possible that extracellular M.tb present in a transferrin-rich environment utilize this pathway for immediate access to iron.…”

Section: Discussionmentioning

confidence: 83%

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Mycobacterium tuberculosis acquires iron by cell-surface sequestration and internalization of human holo-transferrin

et al. 2014

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Mycobacterium tuberculosis (M.tb), which requires iron for survival, acquires this element by synthesizing iron-binding molecules known as siderophores and by recruiting a host iron-transport protein, transferrin, to the phagosome. The siderophores extract iron from transferrin and transport it into the bacterium. Here we describe an additional mechanism for iron acquisition, consisting of an M.tb protein that drives transport of human holo-transferrin into M.tb cells. The pathogenic strain M.tb H37Rv expresses several proteins that can bind human holo-transferrin. One of these proteins is the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH, Rv1436), which is present on the surface of M.tb and its relative Mycobacterium smegmatis. Overexpression of GAPDH results in increased transferrin binding to M.tb cells and iron uptake. Human transferrin is internalized across the mycobacterial cell wall in a GAPDH-dependent manner within infected macrophages.

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Section: Discussionmentioning

confidence: 83%

“…Other studies have demonstrated that ironsaturated transferrin promotes the replication of M. avium within the phagosome 15 . Elevated serum iron and high levels of ironsaturated transferrin are known to have a strong correlation with the exacerbation of tuberculosis in both mouse models and patient studies 3,[16][17][18][19][20] .…”

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confidence: 99%

Mycobacterium tuberculosis acquires iron by cell-surface sequestration and internalization of human holo-transferrin

et al. 2014

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“…We consider that next studies should examine whether this association can be observed in other area and adults as well. Addictively, the studies should be conducted to examine whether hookworm infection causes expansion of the LTBI population and/or directly contributes to TB progression in addition to establishment of infection because there are several reports indicating that helminthic infection is a risk factor for developing TB [27][28][29]. Our study suggests the necessity of the deep studies to understand the relationship between M. tuberculosis and hookworm infection on the prevalence and progression of disease in high-burden countries, including tropical and subtropical areas.…”

Section: Il-10mentioning

confidence: 92%

Relationship between Mycobacterium Tuberculosis and Hookworm Infections among School Children in Mbita, Kenya

Nagi¹

2013

J Trop Dis

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“…The concept of nutritional immunity through metal withholding is largely based on the observations that the iron content of the human diet profoundly affects infectious diseases such as malaria, brucellosis, and tuberculosis (14,15). Iron overload states such as sickle cell anemia and ␤-thalassemia increase the risk of infection (16 -18).…”

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confidence: 99%

Nramp1 and Other Transporters Involved in Metal Withholding during Infection

Wessling‐Resnick

2015

Journal of Biological Chemistry

110

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During the course of infection, many natural defenses are set up along the boundaries of the host-pathogen interface. Key among these is the host response to withhold metals to restrict the growth of invading microbes. This simple act of nutritional warfare, starving the invader of an essential element, is an effective means of limiting infection. The physiology of metal withholding is often referred to as "nutritional immunity," and the mechanisms of metal transport that contribute to this host response are the focus of this review.The rationale for host metal withholding against invading pathogens seems intuitive; restriction of any nutrient required for pathogen survival should combat infection. But why metals? The answer to this question becomes crystal clear when one recognizes that iron is required for nearly all life forms, including pathogenic bacteria, with a few rare exceptions that rely on manganese instead (1-7). Iron is essential for ATP production and other metabolic pathways, but its concentration is limited to avoid production of ROS 2 catalyzed by excess levels of this redox-active metal (8). In some organisms, manganese can substitute for redox-active iron to protect against oxidative stress (9, 10). Moreover, most pathogens require manganese to produce their own superoxide dismutase activity to thwart oxidative killing mechanisms exerted by the host (11-13). Iron and manganese have similar ionic radii, have a divalent charge state under physiological conditions, have similar coordination chemistries, and have cellular concentrations in the micromolar range. Consequently, it comes as no surprise that these two metals also share membrane transporters, despite their different cellular functions and distributions. Restriction of iron and/or manganese provides a broad-spectrum metabolic "antidote" against all pathogenic infections, and the common transport pathways used by these metals present selective targets to limit their availability. Although many other immune responses contribute to the fight against infection, metal withholding represents a major force in host defense with combat controlled through transport.The concept of nutritional immunity through metal withholding is largely based on the observations that the iron content of the human diet profoundly affects infectious diseases such as malaria, brucellosis, and tuberculosis (14, 15). Iron overload states such as sickle cell anemia and ␤-thalassemia increase the risk of infection (16 -18). Hereditary hemochromatosis, an inherited disorder of iron metabolism, is also linked to susceptibility to some pathogens (17, 19 -22). Iron deficiency, on the other hand, is associated with decreased survival of individuals infected with HIV and other agents (23). Still, high iron is positively associated with viral load and mortality in HIV (24 -26), suggesting that an optimal balance of iron is necessary. In general terms, low iron status is protective, whereas elevated iron levels promote infection (27, 28). The complexity of host-pathogen interact...

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Association of Pulmonary Tuberculosis with Increased Dietary Iron

Cited by 162 publications

References 13 publications

Mycobacterium tuberculosis acquires iron by cell-surface sequestration and internalization of human holo-transferrin

Mycobacterium tuberculosis acquires iron by cell-surface sequestration and internalization of human holo-transferrin

Relationship between Mycobacterium Tuberculosis and Hookworm Infections among School Children in Mbita, Kenya

Nramp1 and Other Transporters Involved in Metal Withholding during Infection

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