JAC Advance Access originally published online on October 31, 2006
Journal of Antimicrobial Chemotherapy 2007 59(1):43-50; doi:10.1093/jac/dkl450
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Small-colony variants: a novel mechanism for triclosan resistance in methicillin-resistant Staphylococcus aureus
1 Cardiff School of Biosciences, Cardiff University Park Place, Cardiff CF10 3TL, UK 2 Ciba Spezialitätenchemie Grenzach GmbH, Postfach 1266 D-79630 Grenzach-Wyhlen, Germany
Received 19 August 2006; returned 22 September 2006; revised 26 September 2006; accepted 9 October 2006
*Corresponding author. Tel: +44-29-20875768; Fax: +44-29-20874305; E-mail: day{at}cardiff.ac.uk
Objectives: A little-understood mode of antimicrobial resistance in Staphylococcus aureus is the evolution of a sub-population of small-colony variants (SCVs). SCVs are a cause of persistent and recurring infections refractory to antimicrobial chemotherapy. Following the inadvertent isolation of suspected SCVs growing in the presence of triclosan we set out to evaluate the formation of these colonial mutants and assess their antimicrobial susceptibility.
Methods: SCVs were isolated on Mueller–Hinton agar supplemented with 1 mg/L triclosan. SCV formation frequency was calculated using a selection of both clinical methicillin-resistant S. aureus (MRSA) isolates and methicillin-susceptible S. aureus strains. Antimicrobial susceptibility was assessed and the fabI gene of SCVs was sequenced to ensure resistance was not mediated by mutation of this gene.
Results: We have found in vitro that triclosan can select for S. aureus colonies showing the characteristic SCV phenotype with low-level triclosan resistance and which coincidently have reduced susceptibility to penicillin and gentamicin. Additionally, triclosan-isolated SCVs were shown to have an increased tolerance to the lethal effects of triclosan.
Conclusions: We propose the formation of SCVs by S. aureus is a novel mechanism of resistance to low concentrations of triclosan, which for 25 years has been used widely in the domestic setting in various consumer healthcare products. More recently it has been recommended for the control of MRSA. Consequently, our results identify the potential for treatment failure in infections already notoriously difficult to eradicate. It remains unclear to what extent isolates with decreased susceptibility to triclosan would develop and have the fitness to survive under real world conditions.
Keywords: atypical growth , co-resistance , biocide resistance , mechanisms of resistance
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