On the heels of President Obama’s announcement to increase spending on antibiotic resistance to $1.2B, researchers from Tel Aviv University (TAU) have shown that proteins embedded in bacteria by bacteriophages could lead to a new approach to fight drug resistant microbes.

Bacteriophage T7 lysozyme
Bacteriophage T7 lysozyme/European Bioinformatics Institute

Bacteriophages are viruses that only infect bacteria, and are therefore one of the most common entities in the biosphere.  Because of their selectivity, bacteriophages are being tested for use in treating human bacterial diseases such as Inflammatory Bowel Disease and many infections, albeit with limited success.  Still, they provide an enticing means to study certain strains of bacteria that are not amenable to normal growth or molecular biology methods.

Coevolution of bacteria and viruses has led to steep survival competition, with bacteria evolving a rudimentary “immune system” and viruses producing toxic proteins to stall bacterial evasion mechanisms.  Previous data has shown that viruses encode inhibitors to prevent bacteria from replicating, therefore diverting all energy stores to producing viral proteins.  The researchers noted that some bacteria though evolve around these inhibitors, whereas some inhibitors are too powerful or act too late in viral replication for bacteria to evolve around it.

Using high-throughput sequencing of genomic DNA of bacterial mutants resistant to common antibiotics and bacteriophage inhibitors, the researchers identified two previously known inhibitors as well as a novel inhibitor (‘gene product 0.6’) that prevented bacterial growth and eventually led to cell lysis.  The researchers concluded that protein inhibitors encoded by bacteriophage genes are a newer line in the evolutionary arms race between bacteria and viruses.  This mixed bag of resistance to protein inhibitors by bacteria could lead to targeted therapies for specific antibiotic resistant infections.

The hope is that study of these inhibitors could lead to new small molecule antibiotics that precisely target the same bacterial growth mechanisms as the inhibitory proteins.  “The new technology and our new interdisciplinary collaboration, drawing from bioinformatics and molecular biology, promoted our study more than we could have anticipated,” said Prof. Udi Qimron of the Department of Clinical Microbiology and Immunology at TAU’s Sackler Faculty of Medicine. “We hope our approach will be used to further identify new growth inhibitors and their targets across bacterial species and in higher organisms.”