The good, the bad, and the ugly of metals as antimicrobials

Abstract

We are now moving into the antimicrobial resistance (AMR) era where more antibiotic resistant bacteria are now the majority, a problem brought on by both misuse and over use of antibiotics. Unfortunately, the antibiotic development pipeline dwindled away over the past decades as they are not very profitable compounds for companies to develop. Regardless researchers over the past decade have made strides to explore alternative options and out of this we see revisiting historical infection control agents such as toxic metals. From this we now see a field of research exploring the efficacy of metal ions and metal complexes as antimicrobials. Such antimicrobials are delivered in a variety of forms from metal salts, alloys, metal complexes, organometallic compounds, and metal based nanomaterials and gives us the broad term metalloantimicrobials. We now see many effective formulations applied for various applications using metals as antimicrobials that are effective against drug resistant strains. The purpose of the document here is to step aside and begin a conversation on the issues of use of such toxic metal compounds against microbes. This critical opinion mini-review in no way aims to be comprehensive. The goal here is to understand the benefits of metalloantimicrobials, but also to consider strongly the disadvantages of using metals, and what are the potential consequences of misuse and overuse. We need to be conscious of the issues, to see the entire system and affect through a OneHealth vision.

Keywords: AMR; Antibiotics; Antimicrobial metals; Heavy metals; Metal complexes; Metalloantibiotic; Metallobiotics; Metals; Nanomaterial; One Health; Resistance; Toxic metals.

Fig. 1

Known mechanisms of toxicity of metals towards bacteria. Here we see cartooned a sick bacteria surrounded by the many possibilities for it to be killed by metals. From the top clockwise: Iron-sulfur center damage, replacement of essential metal in protein or enzyme, oxidation of thiols, membrane damage, contact killing on surface, DNA damage, and out competing essential metal import. Blue ball represents the metal atom, squares the essential metal atom. Of course not to scale

Fig. 2

Known mechanisms of resistance/tolerance of metals by bacteria. Here we see cartooned a happy bacteria surrounded by the many possibilities that it can protect itself from metals. From the top clockwise: reduction or organic modification, blocked import of metal atoms, efflux of metal atoms, oxidation repair, metallophores binding up metal atoms, Sequestration by metal binding protein. Blue ball represents the metal atom. Not to scale