Bacterial antimicrobial metal ion resistance

Abstract

Metals such as mercury, arsenic, copper and silver have been used in various forms as antimicrobials for thousands of years with until recently, little understanding of their mode of action. The discovery of antibiotics and new organic antimicrobial compounds during the twentieth century saw a general decline in the clinical use of antimicrobial metal compounds, with the exception of the rediscovery of the use of silver for burns treatments and niche uses for other metal compounds. Antibiotics and new antimicrobials were regarded as being safer for the patient and more effective than the metal-based compounds they supplanted. Bacterial metal ion resistances were first discovered in the second half of the twentieth century. The detailed mechanisms of resistance have now been characterized in a wide range of bacteria. As the use of antimicrobial metals is limited, it is legitimate to ask: are antimicrobial metal resistances in pathogenic and commensal bacteria important now? This review details the new, rediscovered and 'never went away' uses of antimicrobial metals; examines the prevalence and linkage of antimicrobial metal resistance genes to other antimicrobial resistance genes; and examines the evidence for horizontal transfer of these genes between bacteria. Finally, we discuss the possible implications of the widespread dissemination of these resistances on re-emergent uses of antimicrobial metals and how this could impact upon the antibiotic resistance problem. IntroductionMetals and metalloids have a long empirical history of human usage in medicine and agriculture (as reviewed below), despite problems of host toxicity or doubts about their efficacy. Even now, a few toxic metal(loid) compounds are still first-line drugs or preferred-choice chemotherapeutics or antimicrobials, although the use of most of the previously popular antimicrobial metal(loid)s, such as mercury and arsenic/antimony compounds, has been reduced or phased out in the past 50 or so years. Other metals, such as silver and copper, still have limited uses in agriculture and medicine, but are also increasingly being included in consumer products, from clothing to computer keyboards, and are being promoted as useful additions to our arsenal of antimicrobials. Against this background of their current usage, it is reasonable to ask: what is the relevance of antimicrobial metals and bacterial resistances to them to medical microbiology in the twentyfirst century?Any attempt to address this question must be set against the backdrop of widely known problems and opportunities. We are faced with new and emerging opportunistic nosocomial and community-acquired pathogens; and increasing epidemic and pandemic multidrug-resistant (MDR) pathogens. There is a recognition that the antibiotic discovery pipeline has not delivered significant quantities of new antibiotics in the past few decades, and new formulations and uses for antimicrobial metals as weapons in the antimicrobial armoury are being proposed (Department of Health, 2013;Lemire et al., 2013). ...

Survival in amoeba—a major selection pressure on the presence of bacterial copper and zinc resistance determinants? Identification of a “copper pathogenicity island”

“…E. coli express genes encoding ZntA for Zn 2+ efflux, CopA for Cu + efflux, and the CusCBA complex for periplasmic Cu + efflux, but virulent strains have additional copper resistance systems Senftenberg, or Tennessee isolates (Qin et al 2014). This genetic cluster is comprised of two previously reported metal ion resistance determinants, neither of which was realized until recently to be part of a single contiguous gene cluster (Crossman et al 2010;Hobman and Crossman 2015). One, the pco determinant was first isolated from plasmid pRJ1004 from an Australian pig E. coli isolate (Brown et al 1995) and confers copper resistance.…”

Metalloregulator CueR biases RNA polymerase’s kinetic sampling of dead-end or open complex to repress or activate transcription

“…Many others are required for cellular function, such as Zn and Cu, but can be toxic in excess. Cells have thus developed many ways to regulate intracellular metal concentrations (1)(2)(3)(4)(5)(6)(7)(8)(9). Metal-responsive transcriptional regulation is one of them, where metalloregulators respond to intracellular metal ions and regulate transcription of metal efflux, uptake, or other metal homeostasis genes (4)(5)(6)(7)(8)(9).…”

Mercury Resistance and Removal Mechanisms of Pseudomonas sp. Isolated Mercury-contaminated Site in Taiwan

“…Several studies have shown that bacteria of the genus Pseudomonas are highly resistant to the different forms of Hg (Hobman and Crossman, 2015;Ndu et al, 2016) and have been reported in great abundance in waste high in Hg concentrations.…”

“…Although Hg is toxic to both eukaryotic and prokaryotic cells, some microorganisms have developed resistance mechanisms to the metal (Hobman and Crossman, 2015).…”