With drug-resistant, disease-causing microbes spreading worldwide, new types of antibiotics are desperately needed. Now, researchers are closer to a novel strategy for killing bacteria. They've figured out how a dwarf virus bursts out of bacterial cells and hope to borrow the strategy, which has been perfected by the virus over millions of years.
A phage, blue, blocks a complex cascade of cell-building signals to break down a bacterium's wall.
For eons, bacteria have battled particularly tiny viruses called bacteriophages, or phages for short, which infect and kill bacteria but leave humans and other animals alone. The phages infiltrate bacterial cells, where they commandeer the host machinery to make thousands of new phages; then they escape through the bacterial cell wall--killing the host--and spread to infect their next victims. Some phages break out using an enzyme that digests the cell wall. Earlier this year, a team led by microbiologist Ry Young of Texas A&M University in College Station showed that an especially tiny type of phage blocks a bacterial enzyme that builds cell walls. Without it, the bacteria fall apart and allow the phages to make their getaway.
Now, the team has found that another type of dwarf phage also targets a gene responsible for a cell wall-building enzyme. The researchers infected Escherichia coli bacteria with these ultrasmall phages and studied the few strains that survived the infection. Then they transferred snippets of DNA from other strains of E. coli that can't withstand the phages' invasion, to see which genes the E. coli have to harbor for the phages to work their mischief. In the 22 June issue of Science , the team reports that the phages block the enzyme made by a gene called murA, which, like the enzyme targeted by the other small phage, helps assemble cell walls. Drugs that mimic phage proteins could similarly break down bacteria, Young says.
"It's a solid, quality piece of science," says microbiologist Graham Hatfull of the University of Pittsburgh. He cautions that some phage proteins might not work well in the body because they might not reach the infecting pathogen. But Hatfull says there are plenty of other, yet-unstudied phages whose strategies could be adapted for use in antibiotics. As Young says, "it's time to go back into the sewers and find some more."