Abstract
It is essential to understand the mechanisms by which a toxicant is capable of poisoning the bacterial cell. The mechanism of action of many biocides and toxins, including numerous ubiquitous compounds, is not fully understood. For example, despite the widespread clinical and commercial use of silver (Ag), the mechanisms describing how this metal poisons bacterial cells remains incomplete. To advance our understanding surrounding the antimicrobial action of Ag, we performed a chemical genetic screen of a mutant library of Escherichia coli—the Keio collection, in order to identify Ag sensitive or resistant deletion strains. Indeed, our findings corroborate many previously established mechanisms that describe the antibacterial effects of Ag, such as the disruption of iron-sulfur clusters containing proteins and certain cellular redox enzymes. However, the data presented here demonstrates that the activity of Ag within the bacterial cell is more extensive, encompassing genes involved in cell wall maintenance, quinone metabolism and sulfur assimilation. Altogether, this study provides further insight into the antimicrobial mechanism of Ag and the physiological adaption of E. coli to this metal.
Highlights
Metal compounds have been deployed as effective antimicrobial agents [1]
The use of silver (Ag) for antimicrobial purposes is a practice that dates back thousands of years [2] and is still implemented for medical purposes in an effort to curtail the rise of antimicrobial resistant pathogens [3,4,5,6], a threat that has once again surfaced as a clinical challenge [7,8,9,10]
The chemical genetic screen completed in this work provided a method for genome-wide probing of non-essential genes involved in Ag-sensitivity or -resistance in E. coli
Summary
Metal compounds have been deployed as effective antimicrobial agents [1]. Applications of Ag-based antimicrobials include: wound dressings [11] and other textiles [12], antiseptic formulations [13], nanoparticles [14], coatings [15], nanocomposites [16], polymers [17], and part of antibiotic combination therapies [18] Many of these approaches have proven to be effective in controlling and eradicating pathogenic microorganisms. The identity of the cellular targets that are involved in Ag antimicrobial activities are known to a far lesser degree [19] This current knowledge gap hinders the potential utility of Ag-based antimicrobials, and in turn the expansion of this metal as a therapeutic agent
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