Slipping bacteria some silver give old antibiotics new life, scientists at the Wyss Institute for Biologically Inspired Engineering at Harvard University reported June 19 in Science Translational Medicine.

Treating bacteria with a silver-containing compound boosted the efficacy of a broad range of widely used antibiotics and helped them stop otherwise lethal infections in mice. It contributed to making an antibiotic-resistant strain of bacteria sensitive to antibiotics again.

Hippocrates first described the antimicrobial properties of Silver in 400 bc but how it works has been a mystery until now, as a team led by James Collins, a biomedical engineer at Boston University in Massachusetts, has described how silver disrupted bacteria and shown that the ancient treatment could help to deal with the thoroughly modern scourge of antibiotic resistance.
The work is published in Science Translational Medicine.

Collins and his team found that silver — in the form of dissolved ions in water — attacks bacterial cells in two main ways: it makes the cell membrane more permeable, and it interferes with the cell’s metabolism, leading to the overproduction of reactive, and often toxic, oxygen compounds.

Both mechanisms can be harnessed to make today’s antibiotics more effective against resistant bacteria.

Many antibiotics are thought to kill their targets by producing reactive oxygen compounds, and Collins and his team showed that when boosted with a small amount of water dissolved ionic silver these drugs could kill up to 1,000 times as many bacteria.

“…[N]ot only did silver boost the ability of a broad range of commonly used antibiotics so as to stop mice dying of otherwise lethal infections, but it made at least one resistant bacterium succumb to antibiotics again. The addition of silver also broadened the effect of vancomycin, an antibiotic that is usually only effective at killing Gram-positive bacteria like Staph and Strep; aided by silver, it killed Gram-negative bacteria such as those that cause food poisoning and dangerous hospital-acquired infections.”

For example, by adding a small amount of silver to the antibiotic, a powerful synergism occurred, and a urinary tract infection caused by tetracycline-resistant E. coli was successfully eradicated. Silver also helped save the lives of 90 percent of mice suffering from a life-threatening abdominal inflammation by adding it to the antibiotic vancomycin. In the group receiving vancomycin only, a mere 10 percent survived.

The increased membrane permeability also allows more antibiotics to enter the bacterial cells, which may overwhelm the resistance mechanisms that rely on shuttling the drug back out.

That disruption to the cell membrane also increased the effectiveness of vancomycin, a large-molecule antibiotic, on Gram-negative bacteria — which have a protective outer coating. Gram-negative bacterial cells can often be impenetrable to antibiotics made of larger molecules.

Collins says that he and his colleagues saw good results in mice using non-toxic amounts of silver. We’re also encouraging people to look at what features of silver caused the significant effects so that they can look for non-toxic versions,” he says.

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