Biocide tolerance and the harbingers of doom

The mode of action of antimicrobial biocides and the associated resistance mechanisms are generally poorly understood. The historical view that antimicrobial biocides possess broad-spectrum activity has led to a false association with low-target specificity. In fact, many biocides exhibit varying pharmacological activities towards a number of specific cellular targets. Recent reports have demonstrated that sub-lethal concentrations of the anti-bacterial and anti-fungal agent triclosan can select for resistant mutants in Escherichia coli and that this agent specifically targets the enzyme enoyl reductase that is involved in lipid biosynthesis. Triclosan may therefore select for mutants in a target that is shared with the anti-E. coli diazaborine compounds and the anti-tuberculosis drug isoniazid. Although triclosan may be uniquely specific biocide, sub-lethal concentrations of less specific antimicrobial agents may also select for mutations within their least sensitive targets, some of which might be common to therapeutic agents. Misuse of biocides may therefore conceivably have an insidious effect, contributing to the evolution and persistence of drug-resistance within microbial communities and could adversely affect the clinicians' therapeutic arsenal. In this article, we review the problem of antibiotic resistance development and consider the potential clinical implications of inappropriate biocide use. © 2001 Elsevier Science Ltd.