Biochemists at the University of Wisconsin–Madison are using artificial intelligence (AI) to develop new methods for fighting antibiotic-resistant bacterial infections. In a recent study published in the journal Cell Systems, researchers created an AI model that identifies mutations in bacteriophages—viruses that specifically infect bacteria—which could make them more effective at killing harmful bacteria. The study suggests that these AI-guided mutations could make phages up to a million times more effective at targeting certain bacterial pathogens compared to their natural forms. Antibiotic resistance has become a major global health challenge, as many common bacteria have evolved to survive traditional antibiotic treatments. Phage therapy, which uses bacteriophages to kill bacteria, is being explored as a potential alternative. While natural phages have evolved to infect bacteria in ways that help them reproduce, these methods may not always be ideal for completely eliminating harmful bacterial populations. Scientists have therefore sought to engineer phages that are more effective at targeting and destroying disease-causing bacteria. The AI model developed by the Raman Lab was trained using data from extensive research on how mutations in phage proteins affect their ability to infect bacteria. This research focused on proteins that phages use to break through the protective layers of bacterial cells. By analyzing tens of thousands of mutations, the AI was able to detect patterns that could be used to engineer phages with enhanced infection capabilities. The study's findings suggest that AI-guided phage mutations could allow for highly targeted therapies that destroy specific harmful bacteria without affecting beneficial microbes, such as those in the gut. This could be a major step toward safer and more effective phage treatments. The researchers have already begun applying this method to target pathogens responsible for urinary tract infections, bacteria linked to certain diseases, and agricultural pathogens like Salmonella in poultry.