A new resistance mechanism to triclosan which suggests horizontal gene transfer and demonstrates a potential selective pressure for reduced biocide susceptibility in clinical strains of Staphylococcus aureus

Triclosan is one of the best studied biocide and it is widely used in many health care products also to prevent the nosocomial carriage of Meticillin-Resistant-Staphyloccocus aureus (MRSA). Triclosan selectively targets FabI, the NADH-dependent trans-2-enoyl-acyl carrier protein (ACP) reductase, which is an important target for narrow spectrum antimicrobial drug development. In relation to the worldwide growing concern about biocide resistance, we compared in vitro mutants and clinical isolates of S. aureus with reduced triclosan susceptibility. Clinical isolates of S. aureus and laboratory-generated mutants were assayed for MIC and 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 MIC and higher MBC than laboratory mutants. These groups of strains also had few similarities in triclosan resistance mechanism. Molecular analysis identified novel resistance mechanisms linked to the presence of an additional, chromosomally encoded, sh-fabI allele, horizontally transferred 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 be of limited value. More importantly the detection of sh-fabI as 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 spread of a resistance determinant in a human pathogen.