Staphylococcus epidermidis Isolated in 1965 Are More Susceptible to Triclosan than Current Isolates

Sissel Skovgaard, Lene Nørby Nielsen, Marianne Halberg Larsen, Robert Leo Skov, Hanne Ingmer, Henrik Westh, Mark Alexander Webber (Editor)

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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.
Original languageEnglish
Article numbere62197
JournalP L o S One
Volume8
Issue number4
Number of pages8
ISSN1932-6203
DOIs
Publication statusPublished - 2013
Externally publishedYes

Keywords

  • Anti-Infective Agents, Local
  • Drug Resistance, Bacterial
  • Microbial Sensitivity Tests
  • Staphylococcus epidermidis
  • Time Factors
  • Triclosan
  • MULTIDISCIPLINARY
  • CARRIER PROTEIN REDUCTASE
  • SMALL-COLONY VARIANTS
  • CROSS-RESISTANCE
  • ESCHERICHIA-COLI
  • CLINICAL STRAINS
  • MUTANT STRAIN
  • AUREUS
  • BACTERIA
  • MECHANISM
  • INHIBITION
  • Agricultural and Biological Sciences (all)
  • Biochemistry, Genetics and Molecular Biology (all)
  • Medicine (all)
  • alanine
  • cefoxitin
  • messenger RNA
  • phenylalanine
  • triclosan
  • valine
  • amino acid substitution
  • antibiotic sensitivity
  • article
  • bacterial gene
  • bacterium isolate
  • concentration response
  • controlled study
  • DNA sequence
  • drug tolerance
  • fabl gene
  • gene mutation
  • gene overexpression
  • minimum inhibitory concentration
  • mutational analysis
  • nonhuman
  • nucleotide sequence
  • promoter region
  • sequence analysis
  • Bacteria (microorganisms)
  • Eubacteria Bacteria Microorganisms (Bacteria, Eubacteria, Microorganisms) - Endospore-forming Gram-Positives [07810] Bacillus subtilis species
  • Eubacteria Bacteria Microorganisms (Bacteria, Eubacteria, Microorganisms) - Gram-Positive Cocci [07700] Enterococcus faecalis species Streptococcus pneumoniae species
  • Facultatively Anaerobic Gram-Negative Rods Eubacteria Bacteria Microorganisms (Bacteria, Eubacteria, Microorganisms) - Enterobacteriaceae [06702] Escherichia coli species Salmonella genus
  • Facultatively Anaerobic Gram-Negative Rods Eubacteria Bacteria Microorganisms (Bacteria, Eubacteria, Microorganisms) - Vibrionaceae [06704] Vibrio cholerae species
  • Gram-Negative Aerobic Rods and Cocci Eubacteria Bacteria Microorganisms (Bacteria, Eubacteria, Microorganisms) - Alcaligenaceae [06502] Alcaligenes xylosoxidans species
  • Gram-Negative Aerobic Rods and Cocci Eubacteria Bacteria Microorganisms (Bacteria, Eubacteria, Microorganisms) - Pseudomonadaceae [06508] Pseudomonas putida species Pseudomonas aeruginosa species
  • Gram-Positive Cocci Eubacteria Bacteria Microorganisms (Bacteria, Eubacteria, Microorganisms) - Micrococcaceae [07702] Staphylococcus epidermidis species pathogen strain-ATCC 12228
  • Mycobacteria Actinomycetes and Related Organisms Eubacteria Bacteria Microorganisms (Bacteria, Eubacteria, Microorganisms) - Mycobacteriaceae [08881] Mycobacterium genus
  • Staphylococcus epidermidis fabl gene [Micrococcaceae] promoter, expression, mutation
  • enoyl-acyl carrier protein reductase 37251-08-4
  • triclosan 3380-34-5 toxin, bactericide, pesticide
  • 03502, Genetics - General
  • 10062, Biochemistry studies - Nucleic acids, purines and pyrimidines
  • 15002, Blood - Blood and lymph studies
  • 15004, Blood - Blood cell studies
  • 22501, Toxicology - General and methods
  • 31000, Physiology and biochemistry of bacteria
  • 31500, Genetics of bacteria and viruses
  • 39500, Disinfection, disinfectants and sterilization
  • 54600, Pest control: general, pesticides and herbicides
  • Infection
  • Molecular Genetics
  • Pesticides
  • Toxicology
  • adaptation
  • Biochemistry and Molecular Biophysics
  • blood blood and lymphatics
  • NC 004461.1 NCBI nucleotide sequence
  • DNA sequence analysis laboratory techniques, genetic techniques

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