Tired of bacteria making you sick? The Shipman group finds new ways to fight back by making bacteria sick

A groundbreaking new study featured on the June cover of Nature Biotechnology is paving the way for powerful alternatives to antibiotics, especially for drug-resistent bacteria. UCSF scientists have engineered a new, low-cost system to test many variations of phages — viruses that naturally hunt and kill bacteria. Research that was previously laborious and time-consuming, now can be completed quickly and efficiently. 

The world faces an antibiotics pipeline and access crisis, according to the World Health Organization. Antibiotic resistant bacteria were directly responsible for 1.27 million global deaths in 2019 and contributed to nearly 5 million deaths. It makes infections harder to treat and makes other medical procedures and treatments – such as surgery, caesarean sections, and cancer chemotherapy – much riskier.

“One alternative to traditional antibiotics is to use phages, the natural predators of bacteria, to kill strains that are making us sick. This works in some cases, but has been hard to scale up because phages are very specific for the unique species and even individual strain that they target,” explains Seth Shipman, associate professor in the UCSF School of Pharmacy’s Department of Bioengineering and Therapeutic Sciences, and corresponding author of the Nature Biotechnology article. 

Shipman’s team developed new tools to rapidly investigate the interactions between phages and their host bacteria. They built a high-throughput, multiplexed editing system aimed at making many small edits to phage genomes. That allows researchers to quickly test many possible variants and combinations of variants and how they affect interactions with host bacteria.

"We’re trying to figure out how phages know which bacteria to attack, so we can reprogram them to target harmful ones on purpose,” says Shipman, who is part of UCSF Health Innovations Via Engineering (HIVE), which integrates engineering, scientific research, and clinical healthcare to create the newest, early stage technologies that are advancing medicine.

Utimately, this innovation could help researchers design phages on demand to target harmful, drug-resistant bacteria, leading to safer, more precise therapies for patients and new tools for healthcare providers. “It should be easy for other groups to adopt and deploy our methodology,” Shipman says, “and we’ve already heard from multiple labs who are integrating this into their work.”