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 antimi crobial biocides possess broad-spectrum activity has led to a false associa tion with low-target specificity. In fact, many biocides exhibit varying ph armacological activities towards a number of specific cellular targets. Rec ent reports have demonstrated that sub-lethal concentrations of the anti-ba cterial 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 diazabo rine compounds and the anti-tuberculosis drug isoniazid. Although triclosan may be uniquely specific biocide, sub-lethal concentrations of less specif ic antimicrobial agents may also select for mutations within their least se nsitive targets, some of which might be common to therapeutic agents. Misus e of biocides may therefore conceivably have an insidious effect, contribut ing to the evolution and persistence of drug-resistance within microbial co mmunities and could adversely affect the clinicians' therapeutic arsenal. I n this article, we review the problem of antibiotic resistance development and consider the potential clinical implications of inappropriate biocide u se. (C) 2001 Elsevier Science Ltd. All rights reserved.