Table 1.

Mechanisms of action of potentially toxic metals in bacteria.

Toxic metal	Mechanisms of action
Arsenic*, **	As is a toxic metalloid that exists in two major inorganic forms: arsenate and arsenite. Arsenite disrupts enzymatic functions in cells, while arsenate behaves as a phosphate analogue and interferes with phosphate uptake and utilization [64].
Cadmium**	Cd is the most toxic heavy metal, especially against microorganisms. The effects may be summed up under the general headings: “thiol-binding and protein denaturation”, “interaction with calcium metabolism and membrane damage”, “interaction with zinc metabolism”, and “loss of protective function”. The dsbA encoding gene for a product required for disulphite formation, leads to Cd resistance in Gram-negative bacteria [4].
Chromium***	Cr is a micronutrient metal and may be toxic when its concentration exceeds requirements. As a transition metal, it exists in different valency states, ranging from – II to +VI, with Cr(VI) and Cr(III) being the dominant species in the environment. Out of two commonly occurring states, Cr(VI) is toxic to biological systems due to its strong oxidizing potential that invariably damages the cells [65]. Cr(VI) is known to be harmful to all forms of living systems [66], including microorganisms [67].
Copper***	Cu interacts readily with molecular oxygen. Its radical character makes Cu very toxic. Cu toxicity is based on production of hyperoxide radicals and on interaction with cell membranes [4].
Lead	Pb has a low biological available concentration due to its low solubility. Thus, Pb is not extraordinarily toxic to microorganisms [4]. Some forms of lead-salt, like lead acetate or nitrate, induce mutagenicity and DNA breaks at a toxic dose in some bacterial species [68].
Mercury**	Hg toxicity has been attributed to the inactivation of enzymes and interference with other protein functions by the tight binding of mercuric ions to thiol and imino nitrogen groups in these, or the displacement of other metal cofactors from enzymes. Mercuric ions also bind to nucleotides and lipids, interfering with DNA function and contributing to lipid peroxidation. Mercuric ions and organomercurials have the ability to pass rapidly through biological membranes, and organomercurials are highly lipid soluble [69].
Nickel	Four mechanisms of Ni toxicity have been proposed: 1) Ni replaces the essential metal of metalloproteins; 2) Ni binds to catalytic residues of non-metalloenzymes; 3) Ni binds outside the catalytic site of an enzyme to inhibit allosterically; and 4) Ni indirectly causes oxidative stress [70]. Oxidative stress to Ni toxicity in microorganisms is known and some studies have shown that cells subjected to oxidative stress exhibit enhanced DNA damage, protein impairment, and lipid peroxidation, along with increased titres of oxidative stress defence systems; reviewed by [71].
Zinc**	Zn ions inhibit multiple activities in bacterial cells, such as glycolysis, transmembrane proton translocation, and acid tolerance [72]. Trace elements like Zn may be toxic to bacteria and this may be due to their chemical affinity to thiol groups of macro-biomolecules, but may also be dependent on the solubility of the metal compounds under physiological conditions; reviewed by [6].

* Arsenic is not a true metal, but a semi-metal (a semi-metal or metalloid is a chemical element that has the properties of both metallic and non-metallic elements)

** As, Hg, Cd are considered non-essential elements in living organisms.

*** Cu, Zn, and Cr are also essential metals in living organisms.