Small-colony variants: a novel mechanism for triclosan resistance in methicillin-resistant Staphylococcus aureus.
OBJECTIVE
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.
Seaman
Paul F
PF
Cardiff School of Biosciences, Cardiff University, Park Place, Cardiff CF10 3TL, UK.
Ochs
Dietmar
D
Day
Martin J
MJ
D000891:Anti-Infective Agents, Local / Q000494:pharmacology*; D003470:Culture Media; D024881:Drug Resistance, Bacterial; D016106:Methicillin Resistance; D008826:Microbial Sensitivity Tests; D013211:Staphylococcus aureus / Q000187:drug effects*; D014260:Triclosan / Q000494:pharmacology*
D000891:Anti-Infective Agents, Local; D003470:Culture Media; D014260:Triclosan