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An strategy to studying antibiotic proteins produced by bacteriophages using high-throughput genetic screening

Scientists are eager to adopt the bacteria-killing strategies developed by bacteriophages, the viruses that infect bacteria, as conventional antibiotics continue to lose efficiency against changing diseases.

The difficulty of examining individual bacteriophage (phage) proteins and figuring out precisely how the virus uses these weapons to destroy their host bacteria is one of the biggest obstacles in their path. Recent findings from Berkeley Lab, a division of Lawrence Berkeley National Laboratory, may hasten the process.

“We developed a high-throughput genetic screening approach that can identify the part of the bacterial cell targeted by a potent type of phage weapon called ‘single-gene lysis proteins,’” said Vivek Mutalik, a staff scientist in Berkeley Lab’s Biosciences Area and co-author on a new study describing the work in Nature Chemical Biology. Increasing antibiotic use resistance, we urgently need antibiotic alternatives. Some of the smallest phages that we know of code for single-gene lysis proteins (Sgls), also known as ‘protein antibiotics,’ to inhibit key components of bacterial cell wall production that, when disrupted, consistently kill the cell.”

There appears to be at least one type of phage for every known strain of bacteria, and they are thought to be the most abundant biological entities on Earth. In fact, there are an estimated 1031 phage particles on the planet right now, or the equivalent of one trillion phages for every grain of sand. Each of these phages evolve alongside their chosen host strain, allowing them to counter bacterial resistance traits, as they arise, with improved biological weaponry.

This massive abundance, specificity, and efficacy means that there are plenty around to study, and that we should theoretically be able to use phages to control any harmful microbe. Phages are also harmless to non-bacterial cells, another reason they are so appealing as medicines and biocontrol tools.