Iron and Fungal Infections

We saw recently that iron is involved, however unlikely it may seem, in producing dandruff, seborrheic dermatitis, and quite possibly, male pattern baldness. These conditions all have in common that a fungus, Malassezia, is involved. In this short post I want to take a look at the evidence of a connection between iron and fungal infections.

Malassezia

Dandruff and seborrheic dermatitis are both associated with several species of fungus of the genus Malassezia. They are specialized to live on human skin. Like all other microbial pathogens, Malassezia require iron to grow and reproduce, and they obtain iron from their hosts.

Transferrin is the protein molecule in mammals that binds and carries iron. (Ferritin is for iron storage.) Transferrin is at the center of an evolutionary arms race between microbes and primates. Primates try to withhold iron from microbes, and the microbes try to grab it. Each one of them attempts to fight their respective opponents by evolving molecules that have an ever stronger grip on iron.

Iron sequestration provides an innate defense termed nutritional immunity, leading pathogens to scavenge iron from hosts. Although the molecular basis of this battle for iron is established, its potential as a force for evolution at host-pathogen interfaces is unknown. We show that the iron transport protein transferrin is engaged in ancient and ongoing evolutionary conflicts with TbpA, a transferrin surface receptor from bacteria. Single substitutions in transferrin at rapidly evolving sites reverse TbpA binding, providing a mechanism to counteract bacterial iron piracy among great apes…  These findings identify a central role for nutritional immunity in the persistent evolutionary conflicts between primates and bacterial pathogens.

Transferrin inhibits the growth of Malassezia. Adding transferrin to a culture of the fungus withholds iron from it so that it can’t grow. Ciclopirox and salicylate, both iron chelators, also inhibit Malassezia in skin.

Candida

Candida is a genus of fungus with a number of different species and which cause a number of different diseases, including thrush (oral candidiasis), vaginal and skin infections. They can also be invasive and cause blood  and other internal infections. Naturally, Candida requires iron.

Ciclopirox, the iron chelator, inhibits Candida, and the addition of iron reverses the inhibition.

Candida albicans, the major species in this genus, is the only microorganism known to directly exploit ferritin for its iron.

Iron is an essential nutrient for all microbes. Many human pathogenic microbes have developed sophisticated strategies to acquire iron from the host as most compartments in the body contain little free iron. For example, in oral epithelial cells intracellular iron is bound to ferritin, a protein that is highly resistant to microbial attack. In fact, no microorganism has so far been shown to directly exploit ferritin as an iron source during interaction with host cells. This study demonstrates that the pathogenic fungus Candida albicans can use ferritin as the sole source of iron. Most intriguingly, C. albicans binds ferritin via a receptor that is only exposed on invasive hyphae…  Therefore, C. albicans uses an additional morphology specific and unique iron uptake strategy based on ferritin while invading into host cells where ferritin is located.

Cryptococcus neoformans

Cryptococcus neoformans is a fungus that causes an often fatal infection of the meninges and brain, especially in HIV patients. When it senses that iron is available, it grows, and elaborates its pathogenic mechanism.

Iron overload is known to exacerbate many infectious diseases, and conversely, iron withholding is an important defense strategy for mammalian hosts. Iron is a critical cue for Cryptococcus neoformans because the fungus senses iron to regulate elaboration of the polysaccharide capsule that is the major virulence factor during infection. Excess iron exacerbates experimental cryptococcosis and the prevalence of this disease in Sub-Saharan Africa has been associated with nutritional and genetic aspects of iron loading in the background of the HIV/AIDS epidemic. We demonstrate that the iron-responsive transcription factor Cir1 in Cr. neoformans controls the regulon of genes for iron acquisition such that cir1 mutants are “blind” to changes in external iron levels. Cir1 also controls the known major virulence factors of the pathogen including the capsule, the formation of the anti-oxidant melanin in the cell wall, and the ability to grow at host body temperature. Thus, the fungus is remarkably tuned to perceive iron as part of the disease process, as confirmed by the avirulence of the cir1 mutant; this characteristic of the pathogen may provide opportunities for antifungal treatment.

 

There are many other species of fungi that can cause infections, and this is just a quick look at three of them and how they require iron. All other microbes require it as well.

Keeping iron (ferritin) under control may stop these infections from happening. Iron supplementation is known to increase the infection rate and exacerbate their severity.

PS: For more on iron, see my book, Dumping Iron.

PPS: You can support this site by purchasing through my Supplements Buying Guide for Men.

Leave a Comment:

7 comments
bigmyc says January 12, 2017

Great follow up post from a few days ago. As far as iron chelators go, I can only imagine that IP6 would be effective vs. fungus, especially a gut infesting one like candida albicans since the compound is taken internally. Now, if someone has candida overgrowth, it might stand to reason that their ferritin count would dwindle much slower than someone with normal levels of candida. Would you concur with this?

Reply
    P. D. Mangan says January 12, 2017

    No, I don’t think I would. IP6 interacts with iron, not the Candida, so I don’t think the presence of Candida would have an effect.

    Reply
      bigmyc says January 23, 2017

      Allow me to put it another way;
      Candida, along with many gastro-oriented pathogen, utilize a biofilm to protect their colonies from the immune system. These films are comprised of various minerals, calcium, mangesium, etc. I believe that in addition to the organism themselves needing iron, their biofilms are also comprised of this element. So…
      If the IP6 is taken internally, would it not make sense that these biofilms would be one of the very first things that the IP6 would come into contact with and therefore, be drawn to the iron of the biofilms that the candida have created? In this manner, the circulating ferritin wouldn’t so readily be accessed as it would be the iron in the biofilms that might get bonded first.

      I have noticed significant herx events after drinking copious amounts of green tea and turmeric teas…both of these teas, as you know, are iron chelators. Also, by drinking them, they come into immediate contact with candida colonies in the gut (which I have or at least did, in abundance). The idea is that the immune system is only as good as it’s ability to breach the protective layer of biofilm. My theory is that the teas work on the biofilms and as they degrade them, the macrophages and “killer cells” of my immune system, are more able to act directly upon the candida.

      Since IP6 is a powerful iron chelator, would the same not be true of it in respect to candida biofilms?

      Reply
        P. D. Mangan says January 23, 2017

        Yes, I think you’re right. One thing that convinces me of this is that topically applied IP6 actually produces a higher amount in the circulation than an equal amount of oral IP6. Taken orally, it reacts with intestinal contents, including biofilms. IP6 should be a good way of getting rid of biofilms, much like EDTA is.

        Reply
Iron and Fungal Infections says January 13, 2017

[…] post Iron and Fungal Infections appeared first on Rogue Health and […]

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Nathan Viles says January 14, 2017

I’d like to add the many dietary iron chelators you’ve often mentioned that are also associated with longevity: tea, coffee, & turmeric to mention the biggies. If consuming a lot of these, as I do coffee, take care as they also chelate magnesium to a potentially deficient level that for me has caused severe post workout muscle soreness / stiffness that I’ve been able to reduce 90% with a twice a day magnesium supplement. Thanks as always for the life changing info.

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[…] We all get some bacteria inside us regularly, but the body’s natural immunity prevents them from growing and reproducing. One of the most important aspects of this natural immunity is iron withholding. Bacteria require iron to grow, as do all living things, and the body tightly holds on to iron to keep bacteria from procuring it for their own uses. Iron is at the center of an evolutionary arms race between animals and microorganisms. […]

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