Content area
Full Text
REVIEWS
A N T I B I OT I C A LT E R N AT I V E S
Antimicrobial activity of metals: mechanisms, molecular targets and applications
Joseph A.Lemire1*, Joe J.Harrison2* and Raymond J.Turner1
Abstract | Metals have been used as antimicrobial agents since antiquity, but throughout most of history their modes of action have remained unclear. Recent studies indicate that different metals cause discrete and distinct types of injuries to microbial cells as a result of oxidative stress, protein dysfunction or membrane damage. Here, we describe the chemical and toxicological principles that underlie the antimicrobial activity of metals and discuss the preferences of metal atoms for specific microbial targets. Interdisciplinary research is advancing not only our understanding of metal toxicity but also the design of metal-based compounds for use as antimicrobial agents and alternatives to antibiotics.
Certain metals fulfil cellular functions that cannot be met by organic molecules, and these metals are therefore indispensable for the biochemistry of life in all organisms. Specific metal ions are crucial for the structure of cell membranes and DNA; approximately half of all known proteins are predicted to be dependent on metal atoms for their structure and their participation in key cellular processes, such as electron transfer and catalysis1,2. Nonetheless, these essential metals are lethal to all cells when present in excess. Furthermore, certain non-essential metals such as silver (Ag), mercury (Hg) and tellurium (Te) are extremely poisonous to most bacteria and have microbicidal activity at exceptionally low concentrations3,4.
Because of their potent toxicity to bacteria and yeast, particular metals have been used as anti
microbial agents since ancient times (BOX1). Today, antimicrobial metal compounds including metallic surfaces and coatings (which are used, for example, on indwelling medical devices57), chelates and nanomaterials have a multitude of applications in industry, agriculture and healthcare. These innovations were made possible following the discovery that certain metals disrupt antibiotic-resistant biofilms3,8,9, exert synergistic bactericidal activity with other biocides10, inhibit metabolic pathways in a selective manner1113 and kill multidrug-resistant bacteria9,14,15.
So how do metals inhibit microbial growth and kill microorganisms? Here, we use the term metals to collectively describe the transition metals, other metals and metal-loids that poison bacteria primarily through mechanisms
that are independent of hyperosmotic shock. Toxic doses of...