Abstract
The photodynamic effect of hematoporphyrin derivative (HPD) on the viability of penicillin-resistantStaphylococcus 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) onStaphylococcus 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 onStaphylococcus 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 ofS. 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.
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Literature Cited
Bauer, A. M., Kirby, W. M. N., Sherris, J. C., Turck, M. 1966. Antibiotic susceptibility testing by standardized simple disk method. American Journal of Clinical Pathology45:493–496.
Boye, E., Moan, J. 1980. The photodynamic effect of hematoporphyrin on DNA. Photochemistry and Photobiology31:223–228.
Bruns, W. 1973. Methicillin resistance ofStaphylococcus aureus. Contributions to Microbiology and Immunology1:183–192.
Cannistraro, S., Van de Vorst, A. 1977. Photosensitization by hematoporphyrin: ESR evidence for free radical induction in unsaturated fatty acids and for singlet oxygen production. Biochemical and Biophysical Research Communications74:1177–1185.
Coopola, A., Viggiani, E. Salzarulo, L., Rasile, G. 1980. Ultrastructural changes in lymphoma cells treated with hematoporphyrin and light. American Journal of Pathology99:175–192.
Dougherty, T. J., Kaufman, J. E., Goldfarb, A., Weishaupt, K. R., Boyle, D., Mittelman, A. 1978. Photoradiation therapy for the treatment of malignant tumors. Cancer Research38:2628–2635.
Ericsson, H. M., Sherris, J. C. 1971. Antibiotic sensitivity testing. Report of an international collaborative study. Acta Pathologica Scandinavica Section B217:(suppl) 64.
Fiel, R. J., Howard, J. C., Mark, E. H., Datta-Gupta, N. 1979. Interaction of DNA with a porphyrin ligand: evidence for intercalation. Nucleic Acid Research6:3093–3118.
Fiel, R. J., Munson, B. R. 1980. Binding of meso-tetra (4-methyl pyridyl) porphine to DNA. Nucleid Acid Research8:2835–2842.
Kvello-Stenstrom, A. G., Moan, J., Grunborg, G., Eklund, T. 1980. Photodynamic inactivation of yeast cells sensitized by hematoporphyrin. Photochemistry and Photobiology32:349–352.
Malik, Z., Agam, G., Djaldetti, M. 1979. Effect of hemin and protoporphyrin IX on the protein synthesizing activity of human granulocytes, lymphocytes and platelets. Acta Haematologica61:138–143.
Malik, Z., Breitbart, H. 1980. Cross-linking of hemoglobin and inhibition of globin synthesis in reticulocytes induced by photoactivated protoporphyrin. Acta Haematologica64:304–309.
Malik, Z., Djaldetti, M. 1980. Destruction of erythroleukemia myelocytic leukemic and Burkitt lymphoma cells by photoactivated protoporphyrin. International Journal of Cancer26:495–500.
Malik, Z., Djaldetti, M. 1980. Cytotoxic effect of hemin and protoporphyrin on chronic leukemia, lymphocytic leukemia lymphocytes. Experimental Hematology8:867–879.
Moan, J., Pettersen, E. O., Christensen, T. 1979. On the mechanism of photodynamic inactivation of human cells in the presence of hematoporphyrin. British Journal of Cancer39:398–407.
Moan, J., Smedshammer, L., Christensen, T. 1980. Photodynamic effects on human cells exposed to light in the presence of hematoporphyrin. pH effects. Cancer Letters9:327–332.
Moan, J., Waksvik, H., Christensen, T. 1980. DNA single-stranded breaks and sister chromatid exchange induced by treatment with hematoporphyrin and light or by x-rays in human WHIK 3025 cells. Cancer Research40:2915–2918.
Nugent, K. M., Huff, E., Cole, R. M., Theodore, T. S. 1974. Cellular location of degradative enzymes inStaphylococcus aureus. Journal of Bacteriology120:1012–1016.
Popkin, T. J., Theodore, T. S., Cole, R. M. 1971. Electron microscopy during release and purification of mesosomal vesicles and protoplast membranes fromStaphylococcus aureus. Journal of Bacteriology107:907–917.
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Nitzan, Y., Gozhansky, S. & Malik, Z. Effect of photoactivated hematoporphyrin derivative on the viability ofStaphylococcus aureus . Current Microbiology 8, 279–284 (1983). https://doi.org/10.1007/BF01577728
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DOI: https://doi.org/10.1007/BF01577728