Influence of methylation on the antibacterial properties of triclosan in Pasteurella multocida and Pseudomonas aeruginosa variant strains

The opportunistic bacterium Pasteurella multocida is extremely susceptible to the hydrophobic biocide triclosan by virtue of its markedly permeable outer membrane, while the nosocomial pathogen Pseudomonas aeruginosa is intrinsically resistant to levels far exceeding the triclosan aqueous solubility limit. Widespread incorporation of triclosan in health and personal care products has resulted in its concomitant accumulation with metabolites such as methyl triclosan in environmental and biological systems. The present study was undertaken to investigate the possibility that methylation of triclosan may mitigate its antiseptic efficacy in healthcare settings, as well as represent a potential resistance mechanism. Comparative standardised disc agar diffusion and batch cultural turbidimetric bioassays were employed to assess the relationship between triclosan-susceptible or -resistant bacteria and methyl triclosan. A wild-type P. aeruginosa parental strain and a mutant exhibiting a permeable outer cell envelope phenotype were examined in concert with a refractory wild-type strain sensitised to triclosan susceptibility using outer membrane permeabiliser compound 48/80. All organisms examined were resistant to methyl triclosan, and all organisms excluding P. aeruginosa were susceptible to triclosan over a wide concentration range. The permeable outer membrane phenotype in both mutant and chemically sensitised wild-type strains rendered P. aeruginosa susceptible to triclosan, but not to methyl triclosan. These data support the notion that methylation of triclosan renders the compound unable to inhibit the growth of disparate bacterial pathogens in a manner independent of an intact outer membrane. It can also be concluded that biocide modification may contribute to the intrinsic resistance of P. aeruginosa to triclosan.