The Metals

The metals microbes need — and the ones that poison.

A handful of transition metals do almost all of biology's catalytic work. Others have no established role in the human body at all — and several are outright carcinogens. Here is what each essential metal does inside a microbe, followed by the non-essential, toxic metals that reshape the microbiome and drive disease.

Essential Transition Metals

Seven metals do almost all the work.

These seven transition metals are genuinely required for microbial life — the cofactors microbes build their enzymes from. (Nickel, often listed here, is a microbial cofactor too — but it is non-essential and toxic to the human host, so we treat it with the toxic metals below.)

Iron

Atomic no. 26 · The workhorse

The single most important biological redox metal. Iron shuttles electrons through respiration and photosynthesis, and forms the iron–sulfur clusters at the core of central metabolism.

Runs Heme proteins (cytochromes, catalase), [Fe-S] enzymes (aconitase, ferredoxins), ribonucleotide reductase, nitrogenase (with Mo)

Sensed by Fur — the ferric uptake regulator, which alone governs 90+ genes

Scavenged with Siderophores (enterobactin, pyoverdine, pyochelin)

Zinc

Atomic no. 30 · The structural metal

The second most abundant biological transition metal — and, unlike iron, redox-inert, which makes it a safe structural and catalytic cofactor. Bound by roughly 5–6% of a bacterial proteome.

Runs Carbonic anhydrase, proteases, alkaline phosphatase, RNA/DNA polymerases, zinc-finger regulators

Sensed by Zur (uptake) and ZntR (efflux) — tuned to femtomolar free zinc

Scavenged with Zincophores (staphylopine, pseudopaline); imported by ZnuABC

Manganese

Atomic no. 25 · The stress metal

Manganese is the microbe's antioxidant insurance and a frequent "safe substitute" — cells swap it in for iron under oxidative or iron-limiting stress, when a redox-active metal would do damage.

Runs Mn-superoxide dismutase, class Ib ribonucleotide reductase, many metabolic enzymes

Sensed by MntR (DtxR family)

Contested by Calprotectin — the host protein that starves pathogens of Mn

Copper

Atomic no. 29 · The double-edged metal

Copper's potent redox chemistry makes it both extremely useful and extremely dangerous. It sits at the top of the Irving–Williams series, so free copper mismetalates other enzymes — which is exactly why hosts weaponize it.

Runs Cytochrome c oxidase, Cu/Zn-SOD, multicopper oxidases, nitrous oxide reductase, particulate methane monooxygenase

Sensed by CueR, CsoR, CopY (efflux/detox)

Carried by Atx1/CopZ metallochaperones to P-type ATPases

Cobalt

Atomic no. 27 · The B12 metal

Cobalt's biology is dominated by one spectacular molecule: vitamin B12 (cobalamin), in which a cobalt ion sits at the center of a corrin ring. Its synthesis is one of the most complex in all of biochemistry.

Runs B12-dependent methyltransferases, isomerases (methylmalonyl-CoA mutase), some ribonucleotide reductases

Sensed by RcnR (Ni/Co efflux)

Matters for Energy, DNA, lipid and amino-acid metabolism across the microbial world

Molybdenum

Atomic no. 42 · The nitrogen metal

Molybdenum sits at the heart of the planet's nitrogen and sulfur cycles. Its iron–molybdenum cofactor (FeMoco) is the largest known metal cluster in biology.

Runs Nitrogenase (N₂ fixation), nitrate reductase, sulfite oxidase, DMSO reductase families

Delivered as The pterin-based molybdenum cofactor (Moco), or FeMoco in nitrogenase

Matters for Turning atmospheric nitrogen into ammonia — the basis of the biosphere's fixed nitrogen

Tungsten

Atomic no. 74 · The extremophile's metal

The heaviest metal biology uses. Tungsten is concentrated in hyperthermophilic archaea and anaerobes, where its enzymes outperform their molybdenum equivalents at the searing temperatures of hot springs and hydrothermal vents.

Runs Aldehyde:ferredoxin oxidoreductases, formate dehydrogenases

Substitutes for Molybdenum, using the same pterin cofactor scaffold

Matters for Understanding the metal chemistry of early and extreme life

Non-Essential & Toxic Metals

The metals with no place in the body.

These metals are not required for human life — and several, including nickel and hexavalent chromium, are recognized human carcinogens. They poison cells by mismetalating proteins, binding essential thiols, and generating oxidative damage. And because most of an ingested dose is never absorbed, the bulk reaches the gut, where it reshapes the microbiome — the mechanistic heart of the metal–microbiome–disease axis. They are also the metals that heavy-metal certification programs test and limit. Microbes, meanwhile, have evolved dedicated systems to survive — and sometimes exploit — them.

Nickel

Atomic no. 28 · non-essential to humans · carcinogen

A required cofactor for several microbial enzymes — urease and [NiFe]-hydrogenase among them — yet non-essential for humans and a genuine toxicant. Its microbial usefulness is precisely the danger: dietary nickel can license pathogen virulence in the gut, the argument at the center of our review of nickel and necrotizing enterocolitis.

Microbial role Urease, [NiFe]-hydrogenase, CO dehydrogenase — the enzymes that turn nickel into a virulence tool

Health status Nickel compounds are IARC Group 1 carcinogens; the single most common contact allergen; linked to lung, kidney and cardiovascular harm

Aluminum

Atomic no. 13 · non-essential · neurotoxic

The most abundant metal in Earth's crust, with no known biological role. Only about 1% of ingested aluminum is absorbed — so roughly 99% reaches the colon, where it lowers microbial diversity, disrupts the gut barrier, and can raise bacterial pathogenicity. It is also neurotoxic, and infant exposure through formula and processed foods lands squarely in the critical window of microbiome and brain development.

Concern Neurotoxicity; gut dysbiosis and barrier disruption; developmental/infant exposure

Reaches the gut ~99% of an ingested dose passes unabsorbed into the colon

Tin

Atomic no. 50 · non-essential

A tale of two tins. Inorganic tin — leached from unlacquered cans by acidic foods like fruit and pickled vegetables — is poorly absorbed and comparatively low in toxicity. Organotin compounds such as tributyltin are the opposite: among the most potent endocrine disruptors ever released, and toxic to the nervous, hepatic, renal and immune systems at trace levels.

Concern Organotins (tributyltin) — potent endocrine and immune toxicants; inorganic tin from canned foods

Absorption Inorganic tin poorly absorbed; organotins bioavailable and accumulative

Chromium (VI)

Atomic no. 24 · hexavalent · carcinogen

Chromium's toxicity is all about oxidation state. Hexavalent chromium, Cr(VI), is an IARC Group 1 human carcinogen — roughly a hundred times more toxic than trivalent Cr(III) — driving oxidative stress, DNA damage and multi-organ injury. Fittingly, one of the field's cleanup strategies is microbial: bacteria reduce mobile, toxic Cr(VI) to insoluble, far less harmful Cr(III).

Health status IARC Group 1 carcinogen; ~100× more toxic than Cr(III) (which is IARC Group 3)

Detoxified by Microbial Cr(VI) → Cr(III) reduction, used in bioremediation

Arsenic

Metalloid · non-essential · carcinogen

A Group 1 carcinogen and a major contaminant of water and rice. Some microbes detoxify arsenic through the ars operon (reducing and exporting arsenate/arsenite); others respire it. Reciprocally, the gut microbiome modulates how much arsenic the host absorbs and how toxic it becomes.

Handled by ArsR sensor, ArsC reductase, ArsAB export

Microbiome tie The microbiome shapes arsenic metabolism and toxicity

Cadmium

Atomic no. 48 · non-essential · carcinogen

Cadmium mimics zinc and calcium and jams their enzymes. In the gut it reshapes the microbiota and damages the barrier; systemically it targets the kidney and bone. Microbial resistance runs through P-type ATPases and RND efflux — the czc system of Cupriavidus metallidurans is the model.

Handled by CadC sensor, CadA/ZntA, CzcCBA efflux

Concern Kidney and bone toxicity; gut dysbiosis; IARC Group 1

Mercury

Atomic no. 80 · non-essential · neurotoxic

The mer operon reduces toxic Hg²⁺ to volatile Hg⁰ that escapes the cell. But other microbes, via the hgcAB genes, methylate mercury into neurotoxic methylmercury that biomagnifies up the food web — the chemistry behind the Minamata disaster.

Handled by MerR sensor, mercuric reductase; methylated by hgcA/hgcB

Concern Developmental neurotoxicity; biomagnification to fish and humans

Lead

Atomic no. 82 · non-essential · neurotoxic

There is no safe level of lead. It disrupts the same divalent-metal machinery as cadmium, and on exposure it reshapes the gut microbiome — a candidate mediator of its neurodevelopmental harm. Microbes manage lead through efflux and biosorption, properties now explored for lead bioremediation.

Handled by P-type ATPase efflux, biosorption/sequestration

Concern Neurodevelopmental toxicity; gut dysbiosis; no safe threshold

Sources on toxicity Nickel & chromium carcinogenicity: IARC / US National Toxicology Program Report on Carcinogens; chromium mechanisms PMC6737927. Aluminum & the gut microbiome PMC9632190. Tin & organotins ATSDR ToxFAQs.

Turning survival into tools

The very systems microbes use to survive toxic metals are being harnessed for bioremediation and biomining — bacteria that reduce Cr(VI), methylate or demethylate mercury, and biosorb lead — while the metals hosts use as weapons are becoming antibiotics.

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