Trimethoprim-induced structural alterations in Staphylococcus aureus and the recovery of bacteria in drug-free medium.

Bacteriostatic concentrations of trimethoprim, which possibly acts as a DNA-inhibitor, induced the swelling of staphylococci and affected their cell walls, their cytoplasmic membrane and part of their autolytic wall system. Trimethoprim proved to be the first growth-inhibiting drug that did not induce the formation of thickened cell walls in staphylococci. An ultrastructurally important effect of trimethoprim treatment was the appearance of mesosome-like structures which were not fixation artefacts. Additionally, trimethoprim led to the formation of incomplete cross walls, while cross wall initiation continued virtually unaffected. After removal of trimethoprim, extremely fast growth restoration occurred with the formation of new cell wall material underlying the old wall. Afterwards, the old wall material was disintegrated by autolytic processes.