New hope for treating antibiotic resistant bacteria

Parliamentary Yearbook examines new research which suggests that adding silver to antibiotics makes them one thousand times more effective at fighting infections.  It is hoped that the findings could help in the fight against antibiotic resistance.

Silver has been used as an antimicrobial for centuries. Despite this widespread use, the exact mechanism of its action has remained unclear. New research by a team of American scientists has been published in the journal Translational Medicine which identifies exactly how silver fights bacteria in a number of ways.  The research suggests that adding silver to existing anitbiotics could help strengthen the antibiotic arsenal for fighting bacterial infections.

Silver has been used to fight infections for thousands of years.   Hippocrates first described its antimicrobial properties in 400 b.c.; noting its special ability to preserve food and water. Today silver is routinely used to treat and prevent infections and can be found in wound dressings and catheters but the source of this precious metal’s antibacterial properties has remained a mystery.  In this latest research, James Collins, of the Wyss Institute for Biologically Inspired Engineering at Harvard University and colleagues from Boston University, describe a number of ways in which silver fights bacteria.   

The study is important because it investigates the effects of silver on E.coli, a Gram-negative bacterium. The most difficult types of infections to are those that involve Gram-negative bacteria, like E.coli and Salmonella.  These bacterial strains have an almost impenetrable cell wall that shields them from antibiotics.  They are resistant to multiple drugs and are increasingly resistant to most available antibiotics.  Gram-negative bacteria have built-in abilities to find new ways to be resistant and can pass along genetic materials that allow other bacteria to become drug-resistant as well. 

The research team conducted a series of experiments using E.coli in petri dishes and in live mice suffering from urinary tract infections.  The study aimed to investigate exactly how silver kills Gram-negative bacteria. 

The findings show that silver mounts a multi-targeted attack on the bacteria which breaks down their cells walls and increases their production of reactive oxygen species (ROS), chemically reactive molecules containing oxygen.  An increase in ROS molecules, caused by traditional antibiotics or silver automatically triggers bacterial cell death.

The researchers subsequently investigated the effects of combining silver with a range of antibiotics. They found that the silver acted as a sort of Trojan horse.  It helped to deliver the treatment beyond the cells’ walls which allowed the antibiotic to maximally damage the bacterial cells. 

The findings were remarkable.  They showed that antibiotics, when combined with silver, were 10 to 1,000 times more effective at fighting infections than when antibiotics alone were used. Even at small doses, silver made the E.coli up to one thousand times more sensitive to gentamycin, ofloxacin and ampicillin; three widely used antibiotics.

In further tests with mice, they found that a E.coli urinary tract infection that was resistant to tetracycline finally succumbed when the antibiotic was combined with silver.  Similarly, they found that, combined with silver, vancomyin saved the lives of 90% of mice with life-threatening peritonitis. Treated with vancomycin alone, 90% of the mice died.

The doses of silver used used in the experiments were tested to ensure they were not toxic.  The team showed that levels were too low to harm the mice. It was also confirmed that levels used did not harm human cells.

The researchers believe that silver may enable existing antibiotics to treat a wider range of infections, including those to which microbes have become resistant.

Commenting on the research, Jim Collins said:  “We’re keen to explore how smart drug-delivery nanotechnologies being developed at the Wyss could help deliver effective but nontoxic levels of silver to sites of infection.”

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