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Antimicrobial resistance, in which germs like bacteria and fungi no longer respond to medicines, is a rising global threat. When antibiotics and other drugs become ineffective, infections can become difficult or impossible to treat, leading to an increase in the spread and severity of disease.

In a new , a team of researchers at the discovered a novel approach that may revolutionize the fight against antimicrobial resistance.

For the study, the research team investigated the use of phage therapy鈥攖he use of viruses, or phages, to target and kill bacteria鈥攖o help patients with cystic fibrosis, a disease in which antimicrobial resistance is a significant issue. The team pioneered a strategy to select phages that not only kill bacteria that cause infections but also weaken surviving bacteria to become less virulent or less resistant to antibiotics.

The study found improved lung function, reduced sputum P. aeruginosa鈥攐ne of the most prevalent infection-causing bacteria in cystic fibrosis鈥攁nd evidence of phage-resistant bacteria having reduced pathogenicity in the nine adults treated with this therapy. The therapy was safely delivered by nebulization.

There are millions of people worldwide who are suffering from drug-resistant infections, said , associate professor in Yale School of Medicine鈥檚 (Yale PCCSM) and medical director of the Center for Phage Biology and Therapy, who is the corresponding author of the study.

鈥淲e currently have a lack of effective antibiotics, and the World Health Organization predicts that by 2050, we鈥檒l have more deaths from antimicrobial resistance than from chronic diseases like cancer and diabetes,鈥� he said. 鈥淭his compassionate treatment is an opportunity for us to use phage therapy for patients with life-threatening infections and no other treatment options.鈥�

, Rachel Carson Professor of Ecology and Evolutionary Biology and director of the Center for Phage Biology and Therapy, emphasized Koff鈥檚 understanding of the capability of infecting bacteria to evolve resistance to administered phages.

鈥淗e continues to advocate that personalized treatments and clinical trials in phage therapy must address this possible limitation, so that evolved phage resistance in bacteria is either minimized or steered down a path which coincides with reduced pathogenicity, thus improving patient outcomes,鈥� Turner said.

The study highlights the power of Yale鈥檚 integrated basic, translational, and clinical science teams, said , Boehringer Ingelheim Pharmaceuticals, Inc. Professor of Medicine and chief of Yale PCCSM. 鈥淎ddressing microbial drug resistance is a critical unmet need, and the team at the Center for Phage Biology and Therapy at Yale is at the frontline of this battle,鈥� he said.

Members of the research team have had conversations with the U.S. Centers for Disease Control and Prevention and the Cystic Fibrosis Foundation about setting up centers for phage therapy around the U.S. The Center for Phage Biology and Therapy at Yale is poised to lead the way in developing a U.S.-based system of coordinated care for patients who need compassionate treatment, Koff said.

The goal is to develop partnerships across and beyond Yale to treat patients locally and to develop a standard that can be used nationwide, he said.

In addition, the team is working with countries in Europe and South America to establish national phage therapy programs.

鈥淲hen we look at the trajectory of antimicrobial resistance, we see a pandemic that could happen in the next 30 years,鈥� Koff said. 鈥淏y using phage therapy to help patients with cystic fibrosis, we are also finding solutions to address a growing crisis.鈥�

The first authors of this study are , scientific director for the Center for Phage Biology and Therapy, , Yale PCCSM instructor, and , postdoctoral associate in the Turner Lab.

Other Yale authors of this study include , Isabel Ott, , Silvia W眉rstle, , , , Zachary Harris, , , , Quynh-Anh Mai, and .

To learn more about phage research at Yale, visit the .