A novel resistance mechanism to triclosan that suggests horizontal gene transfer and demonstrates a potential selective pressure for reduced biocide susceptibility in clinical strains of Staphylococcus aureus.
The widely used biocide triclosan selectively targets FabI, the NADH-dependent trans-2-enoyl-acyl carrier protein reductase, which is an important target for narrow-spectrum antimicrobial drug development. In relation to the growing concern about biocide resistance, we compared in vitro mutants and clinical isolates of Staphylococcus aureus with reduced triclosan susceptibility. Clinical isolates of S. aureus as well as laboratory-generated mutants were assayed for minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) phenotypes and genotypes related to reduced triclosan susceptibility. A potential epidemiological cut-off (ECOFF) MBC of >4 mg/L was observed for triclosan in clinical isolates of S. aureus. These showed significantly lower MICs and higher MBCs than laboratory mutants. These groups of strains also had few similarities in the triclosan resistance mechanism. Molecular analysis identified novel resistance mechanisms linked to the presence of an additional sh-fabI allele derived from Staphylococcus haemolyticus. The lack of predictive value of in-vitro-selected mutations for clinical isolates indicates that laboratory tests in the present form appear to be of limited value. More importantly, detection of sh-fabI as a novel resistance mechanism with high potential for horizontal gene transfer demonstrates for the first time that a biocide could exert a selective pressure able to drive the spread of a resistance determinant in a human pathogen.
Dipartimento di Biotecnologia, Università di Siena, Siena, Italy.
Maria Laura
ML
Ciusa
Leonardo
L
Furi
Daniel
D
Knight
Francesca
F
Decorosi
Marco
M
Fondi
Carla
C
Raggi
Joana Rosado
JR
Coelho
Luis
L
Aragones
Laura
L
Moce
Pilar
P
Visa
Ana Teresa
AT
Freitas
Lucilla
L
Baldassarri
Renato
R
Fani
Carlo
C
Viti
Graziella
G
Orefici
Jose Luis
JL
Martinez
Ian
I
Morrissey
Marco Rinaldo
MR
Oggioni
D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D004202:Disinfectants / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D022761:Gene Transfer, Horizontal; D005838:Genotype; D006801:Humans; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D012641:Selection, Genetic; D017422:Sequence Analysis, DNA; D013203:Staphylococcal Infections / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000302:isolation & purification; D014260:Triclosan / Q000494:pharmacology*
D004269:DNA, Bacterial; D004202:Disinfectants; D014260:Triclosan