| ABSTRACT:
Eddy Ruben and Rotem Sorek of Berkeley Lab have discovered a new method for mining microbial genomes for “killer” proteins that can be used as antibiotics. This new method, which may overcome the antibiotic-resistance of bacteria, isolates antimicrobial proteins from microbial genomes. These proteins may be used to create antibiotics for human and veterinary medicine, food preservatives, probiotics that may be used for dietary supplements, and crop management aids such as fertilizers.
The new method is a by-product of the genome-sequencing process, where draft sequenced genomes contain gaps due to DNA fragments that cannot be successfully grown in bacteria. The Berkeley Lab researchers discovered that these gaps occur because of genes that are toxic to the bacteria used for genome sequencing. They searched for such genes in 30 microbial genomes, and collected 125 proteins from genomic regions that had zero or low coverage in clones. After testing the proteins for having antimicrobial (i.e., bactericidal or bacteriostatic) behavior against E. coli and other pathogenic bacteria, they found that 78 of these proteins are toxic when expressed in E. coli. Because of their toxic effects on the growth of E. coli, it is likely that these 78 proteins may be used to develop effective antibiotics.
The Berkeley Lab method also offers promising advancements for antimicrobial studies overall, as it overcomes the problem of genes that are toxic to bacteria and unclonable in E. coli, and thus are difficult to mine for antimicrobial proteins. By creating a new method that identifies unclonable regions in sequenced (“finished”) microbial genomes, retrieves killer genes residing in these regions, and demonstrates their proteins’ toxicity to E. coli and other pathogenic bacteria, the Berkeley Lab inventors have discovered a new way to create more effective antibiotics. |
