Silver Sulfadiazine: Effect on the Growth and Metabolism of Bacteria

Abstract

Even though the addition of silver sulfadiazine (AgSu) to purified deoxyribonucleic acid (DNA) results in the formation of AgSu-DNA complexes, no such complexes were detected in bacteria treated with AgSu. AgSu blocked macromolecular syntheses in treated bacteria, DNA synthesis being slightly more sensitive to this inhibitory action. The ribosomes, ribonucleic acid, and DNA isolated from treated cells were normal qualitatively. Bacteria deficient in DNA polymerase were not more sensitive than their parent strain to the lethal action of AgSu. Radioactive AgSu was localized mainly in the cytoplasmic membrane fraction of treated cells.The proven efficacy of silver sulfadiazine (AgSu) in the treatment of Pseudomonas infections in burns (8-12, 14, 28, 31) has made a study of its mechanism of action desirable. It has been suggested (11), by analogy with the in vitro complex formation between silver nitrate and deoxyribonucleic acid (DNA;6,15,30,l 32), that complex formation between AgSu and DNA was also the basis of its antibacterial action in vivo. Studies on the in vitro interaction of AgSu and DNA have shown (24) that an AgSu-DNA complex was indeed formed, but that it was very different from the AgNO3-DNA complex. The properties of the AgSu-DNA complex have been characterized (24). The present study was undertaken to determine whether such complexes were also formed in vivo upon exposure of bacteria to AgSu and whether they could account for the biological activity of AgSu. It Growth of bacteria. At first, attempts were made to grow P. aeruginosa in media poor in chloride to prevent the transformation of AgSu into insoluble AgCl. However, when it was found (24) that AgSu did not ionize and that no insoluble AgCl was formed, bacteria were grown in medium HA (20). For determining the number of viable bacteria, serial dilutions of the cultures were spread onto Columbia-base agar plates (BBL); these were incubated for 16 hr, and colonies were then counted.E. coli W31 10 and p3478 were grown on medium HA supplemented with thymine (5 ,ug/ml). Because of the poor plating efficiency of E. coli p3478 on Columbia-base agar (20), the bacteria were spread on agar plates containing medium HA and thymine.Metabolic techniques. Techniques for determining the incorporation of specific precursors of DNA, ribonucleic acid (RNA), and protein into acidinsoluble products have been described previously (16,(21)(22)(23).Bacterial DNA was prelabeled by growing bacteria in the presence of 3H-thymidine for several generations, harvesting the cells, and resuspending them in fresh medium. The bacteria were then incubated with aeration for 30 min to deplete the pool of radioactive precursor. A portion of the culture was then exposed to AgSu (5,ug/ml) for 1 hr.Bacterial DNA was extracted from protoplasts (13) by the procedure of Bode and Kaiser (3), which was modified to include several extractions of the material at the interphase to increase the recovery of DNA.Procedures for the physical-chemical characterization of macromolecules have bee...

Electrical methods of controlling bacterial adhesion and biofilm on device surfaces

“…This, coupled with electrode corrosion would be used to explain any bacteriostatic action in other electrodes. The silver ion was suggested as the reason for such a strong bactericidal effect and other research on the antibacterial effects of silver sulfadiazine would appear to support this [45,46]. Electrically injected silver ions in this experiment were shown to be at least as effective as an antibiotic.…”

Silver hydrogel urinary catheters: Evaluation of safety and efficacy in single patient with chronic spinal cord injury

“…The activity of silver against multiresistant strains, including methicillin sodium-resistant staphylococci and vancomycin-resistant enterococci is particularly important. This action is postulated to be mediated by binding of the silver ions to cellular DNA [28] and the cell membrane [29]. Resistance to silver has been reported in a small number of organisms, including some strains of Proteus mirabilis, Enterobacter cloacae, Citrobacter freundii, and Klebsiella pneumoniae [30].…”

Effects of silver sulphadiazine on the production of exoproteins by Staphylococcus aureus

“…Sulphadiazine potentiates the action of AgSD and it has been suggested that this may be due to a reduced degree of ionisation of the AgSD, thus slowing the release of Ag into the medium [18]. Although AgSD interacts irreversibly with DNA to form a complex in vitro [23], this does not appear to be its mode of action in vivo and Ag 2 ion is the active agent [24]. Silver ions react with DNA in vitro, ®rstly in a weak interaction then strongly with the silver ions becoming incorporated by bonding between the base pairs [25].…”

“…Silver ions react with DNA in vitro, ®rstly in a weak interaction then strongly with the silver ions becoming incorporated by bonding between the base pairs [25]. Although it has been suggested that binding to DNA is the mode of action in vivo [18], other workers suggest that Ag 2 binds preferentially to external cell structures and that only small amounts are bound to DNA [24]. Cells of S. aureus treated with AgSD were enlarged, some retraction of the cytoplasmic membrane from the cell wall was seen and division planes between bacteria became indistinct, supporting the view that the effect is on external cell structures [26].…”