Could designer antibiotics hit bugs where it hurts?
By Martin Brookes SINGLE genes that infectious bacteria depend on for their survival have come to light. The researchers who made the discoveries say their technique could lead to a new generation of antibiotics. Resistance to antibiotics is increasing among our microbiological foes. Existing antibiotics can be tweaked to outwit the bacteria, but they soon develop resistance to the new line of attack. “We need totally new approaches,” says Hannes Loferer of Genome Pharmaceuticals in Munich. One alternative is to find genes that are essential for the survival of bacteria but not humans, and to target these genes with new drugs. Loferer and his colleagues reasoned that genes that are common to many species of bacteria would be likely candidates. Biologists have long suspected that genes that are widely conserved are vital for life. To date, the entire genomes of 14 species of bacteria have been sequenced, including that of Mycoplasma genitalium, one of the simplest bacteria, which has only about 600 genes. Loferer’s team compared M. genitalium’s DNA sequence with that of Escherichia coli and found that they have 26 genes in common. “These genes were also conserved in all the other sequenced species,” says Loferer. To identify which of these genes are essential to E. coli, the researchers engineered 26 mutant strains that each lacked one of the genes. They then tested the mutants to see if they could survive. The team say in this month’s Nature Biotechnology (vol 16, p 851) that of the 26 genes, six were found to be essential for survival. Four of these were not essential to yeast, and may well be nonessential to humans, suggesting that they may be good targets for future antibiotics. “This is the first example of using comparative genomics to look for new targets for antibiotics,” says Loferer. “In the future,