Is the ultrastructural damage caused by subinhibitory concentrations of trimethoprim and sulphadiazine part of their normal mechanism of action

The test organism was Escherichia coli 1810 which was highly resistant to trimethoprim (TMP). Electron microscopy (EM) of cells grown in the presence of subinhibitory concentrations of 300 μg/ml sulphadiazine (SD) and/or 300 μg/ml TMP indicated marked structural damage. No effect on the outer membrane (OM) or ultrastructure of E. coli 1810 was observed with 7.68 μg/ml TMP and/or 16.9 μg/ml SD. Concentrations of antibacterials affecting the ultrastructure of the bacterial cells of resistant and sensitive E. coli as determined by EM, were shown by a permeability probe (Triton X-100) to alter the OM permeability and to partially inhibit growth of E. coli 1810 cultures. It was concluded that, since the action of SD and TMP, singly and in combination, on the cell structure of E. coli 1810 took place only at concentrations approaching the respective MICs, then this was a part of their normal mechanisms of antibacterial action.