Precious metal holds promise as powerful agent for use against superbugs such as MRSA, writes Anne Bermingham.
Silver is widely admired for its stunning visual appearance, but perhaps less well known is that this bright white metal has an extraordinary healing capability. In its ionic form, silver is a powerful antimicrobial agent that can offer new ways to fight infectious disease.
Using silver to create a new class of antimicrobial drug is the goal of a multidisciplinary research team that includes scientists from the Dublin Institute of Technology, NUI Maynooth and the Institute of Technology, Tallaght.
"Elemental silver and silver salts have been used successfully for decades but lost favour as antibiotics became a popular treatment for infection," says Dr Michael Devereux, co-ordination chemist and senior lecturer at the Dublin Institute of Technology (DIT).
Therapeutic silver agents work by releasing a very precise stream of silver ions into the infection site. "It's like firing high-calibre silver bullets aimed at medicinal targets," he explains.
The increasing resistance to antibiotics and the emergence of "superbugs" has made finding new metal-based treatments a matter of pressing importance, says Dr Devereux, who worked with chemist Dr Denis O'Shea in DIT's Inorganic Pharmaceutical and Biomimetic Research Group to select different silver compounds for synthesis. The initial goal was to discover how different structural variations of silver-based compounds would affect the metal's antimicrobial activity.
Creating structures that are stable and are capable of providing a slow release of silver ions are important factors that affect the performance of silver antimicrobials. To achieve this, the research team used a type of organic molecule called a "chelating agent".
The word "chelate", from the Greek word for claw, describes how the silver ion is firmly gripped in place by the surrounding organic molecule, which increases the stability of the whole compound. Chelation enables a very slow release of silver ions, which is necessary as silver only has effective antibacterial activity at low concentrations.
The research team has now generated a whole range of these silver complexes that show promising results. They found that some of the new complexes were 60 times more active against fungal pathogens than compounds containing simple free silver ions. Significantly, some of the complexes that incorporated salicylic acid and ammonia were found to be twice as effective against MRSA, and 100 times more effective against the fungal pathogen Candida Albicans than the clinical silver agents currently used.
One apparent setback was that although these silver complexes showed strong antimicrobial activity, they were also "cytotoxic", poisonous to healthy human cells. "At first this seemed like a disappointing result but what we quickly realised was that if they were cytotoxic it was possible that they might have another application," says Dr Devereux.
Cytotoxic agents are conventionally used for treating cancer cells, so the team carried out experiments that looked at anti-cancer activity. "We then found that some of these compounds are 17 times more active against selected cancer cell lines in-vitro than the current metal-based drug cisplatin which is used against ovarian and testicular cancer," he says.
The new goal for the team is determining how these compounds kill cancer cells. The team are also looking at ways of increasing the selectivity of the silver antimicrobials by reducing their cytotoxicity but maintaining their excellent antibacterial and antifungal properties.
Members of the multidisciplinary team include Dr Malachy McCann and Dr Kevin Kavanagh from NUI Maynooth and Dr Denise Egan, Dr Maureen Walsh and Dr Bernie Creaven from IT Tallaght Dublin.
The work is funded by the Technological Sector Research Programme under the European Social Fund 2002. The work is also assisted by the Irish National Development Plan 2000-2006, and the European Regional Development Fund.