Abstract
Since its introduction to the market in the 1970s, the synthetic biocide triclosan has had widespread use in household and medical products. Although decreased triclosan susceptibility has been observed for several bacterial species, when exposed under laboratory settings, no in vivo studies have associated triclosan use with decreased triclosan susceptibility or cross-resistance to antibiotics. One major challenge of such studies is the lack of strains that with certainty have not been exposed to triclosan. Here we have overcome this challenge by comparing current isolates of the human opportunistic pathogen Staphylococcus epidermidis with isolates collected in the 1960s prior to introduction of triclosan to the market. Of 64 current S. epidermidis isolates 12.5% were found to have tolerance towards triclosan defined as MIC≥0.25 mg/l compared to none of 34 isolates obtained in the 1960s. When passaged in the laboratory in the presence of triclosan, old and current susceptible isolates could be adapted to the same triclosan MIC level as found in current tolerant isolates. DNA sequence analysis revealed that laboratory-adapted strains carried mutations in fabI encoding the enoyl-acyl carrier protein reductase isoform, FabI, that is the target of triclosan, and the expression of fabI was also increased. However, the majority of the tolerant current isolates carried no mutations in fabI or the putative promoter region. Thus, this study indicates that the widespread use of triclosan has resulted in the occurrence of S. epidermidis with tolerance towards triclosan and that the adaptation involves FabI as well as other factors. We suggest increased caution in the general application of triclosan as triclosan has not shown efficacy in reducing infections and is toxic to aquatic organisms.
Highlights
Triclosan is a synthetic broad spectrum biocide that was introduced to the market in the early 1970s [1]
Old and current S. epidermidis isolates had the same MIC50 (MIC required to inhibit the growth of 50% of isolates) of 0.0625 mg/l and for the old isolates the MIC90 (MIC required to inhibit the growth of 90% of isolates) was 0.0625 mg/l
This study indicates that wild-type S. epidermidis has changed their population structure to adapt to the widespread use of triclosan
Summary
Triclosan is a synthetic broad spectrum biocide that was introduced to the market in the early 1970s [1]. In low concentrations triclosan inhibits the growth of many bacteria and higher concentrations can be bactericidal [2,3]. It is widely used as an antiseptic, disinfectant and preservative in clinical settings and in various consumer products including cosmetics, plastic materials, toys and textiles [4]. Triclosan is excreted in the urine and has been found in human urine (2.4–3790 mg/l), plasma (0.01–38 mg/l) and breast milk (0.018–0.95 mg/l). The extensive use in human products has led to accumulation in the environment with concentrations of 20– 133,000 mg/kg dry-weight in biosolids from wastewater treatment plants. In the ng/l range, have been found in lakes, rivers, seawater and drinking water. Toxicological studies indicate that triclosan is not toxic for mammals, triclosan has an estimated bioaccumulation factor of more than 1000 in algae and can be highly toxic to green algae. [4,5,6]
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