Bacteria have a weakness: silver. The precious metal has been used to fight infection for thousands of years - Hippocrates first described its antimicrobial properties in 400 BC - but how it works has been a mystery. Now, a team led by James Collins, a biomedical engineer at Boston University in Massachusetts, has described how silver can disrupt bacteria, and shown that the ancient treatment could help to deal with the thoroughly modern scourge of antibiotic resistance. Collins and his team found that silver - in the form of dissolved ions - attacks bacterial cells in two main ways: [silver] 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 could potentially be harnessed to make today's antibiotics more effective against resistant bacteria, Collins says. 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 silver these drugs could kill between 10 and 1,000 times as many bacteria. 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.