Effect of photoactivated hematoporphyrin derivative on the viability of Staphylococcus aureus

The photodynamic effect of hematoporphyrin derivative (HPD) on the viability of penicillin-resistant Staphylococcus aureus is described. Growth rate of the bacteria was markedly reduced by exposure to light and HPD. Staphylococcus viability was decreased by 80% in 3 h of growth even at low HPD concentration (12 μg/ml). A synergistic killing effect of HPD, light, and penicillin (10 μg/ml) on Staphylococcus aureus was demonstrated, although the bacteria were originally resistant to 100 μg/ml penicillin. A residual viability of only 3% was found by growth in medium containing this drug combination. The surviving bacteria after 3 h of treatment were sensitive even to 1 μg penicillin/ml. The mechanism of HPD action on Staphylococcus is composed of two steps: i) penetration of HPD into the bacterial cell, which may be accomplished in the dark with no harm to the cells; ii) damaging of the bacterial cell upon photoactivation. The photoactivated HPD completely inhibited thymidine incorporation into the bacterial DNA. This effect was accompanied by inhibition of RNA and protein synthesis, which was parallel in extent to the reduction in growth rate. Electron microscopic examination of S. aureus exposed for 3 h to HPD and light showed the appearance of well-developed mesosomes in the bacterial cells. None of these effects was observed on Gram-negative bacteria.