Taking a Cancer Treatment Approach to New Antibiotic Development

We are continuing our new series, Media Day, where we spotlight individual medical institutions and infectious disease (ID) programs. Today, we spotlight UC San Diego’s Skaggs School of Pharmacy and Pharmaceutical Sciences and the university’s extensive research programs and community-based health programs to serve the local population.

Victor Nizet, vice chair for Basic Research in the Department of Pediatrics, chief of the Division of Host-Microbe Systems and Therapeutics, UC San Diego, says antibiotics—as currently developed—are becoming less reliable, and there can be some issues associated with taking them.

“When you take antibiotics, not only do you kill the pathogen…but you kill a lot of the good bacteria as collateral damage,” Nizet said. “And when we lose those good bacteria, we might set ourselves up for different problems. It appears that, especially early in life, if you see take too many antibiotics, you might have a higher risk of metabolic disorders, obesity, allergy, and autoimmune diseases.”

He would like to take an approach similar to cancer treatment development.

“I have a strong belief that we need to step back and think about the whole host pathogen interaction, the way the microbe is interacting with the immune system,” Nizet said. “And just like cancer, doctors have made tremendous advances in recent years by harnessing the power of the immune system and immunotherapies like checkpoint inhibitors and CAR T cells that have created much better outcomes in diseases. My lab is particularly interested in understanding how antibiotics work in the body, together with the immune system, and also coming up with novel therapies that work through the immune system.”

Nizet and fellow researchers demonstrated how this concept works and how antibiotics can continue to have utility as they work in concert with the immune system to kill the bacteria, despite what in-vitro findings might show. For example, his team worked with the University of Texas at Tyler examining drug-resistant infections. Their work examining bacterial pathogenesis showed that the antibiotic, colistin, which is often characterized as the treatment of “last resort” for severe infections, remained effective against a dangerous class of antibiotic-resistant bacteria when tested in conditions that better mimic the human body.¹

Specifically, they examined the mobilized colistin resistance (mcr) gene, which is a form of resistance that can rapidly spread among bacteria. The presence of the mcr gene renders many significant Gram-negative pathogens, like E coli and Klebsiella pneumoniae, resistant to colistin in the standard lab testing protocols performed in test tubes and petri dishes. Their paper on this was published in The Journal of Clinical Investigation.¹

“What we discovered is that those genes make the bacteria resistant in the laboratory, on the test tube…but if you study these strains in the context of the body, colistin collaborates with our immune system to kill the bacteria, so we're inadvertently declaring the bacteria resistant when the drug still has utility in the body. We prove that in human blood, and we prove that in mouse infection models,” he said.

The existing testing exhibits shortcomings says Nizet. “These results don’t mean we should throw out current guidelines,” Nizet said in previous interview. “But they do underscore the need to modernize antimicrobial susceptibility testing. Standard lab tests don’t account for the synergy between drugs and our immune system. This can make us underestimate a drug’s true potential.”¹

“We want to usher in a new era of antibiotic evaluation, where we consider the immune system. We don't just study it in a vacuum in terms of drug repurposing," he said.

 In the next episode, Nizet provides more insights on this line of antibiotic development as well as looking at nanotherapeutics and vaccines for combating antibiotic-resistant pathogens.

Reference
1.Pritchett J. Rethinking Resistance: New Life for a “Last Resort” Antibiotic. UC San Diego School of Medicine. Accessed September 22, 2025.
https://medschool.ucsd.edu/about/news/archive/2025/06-25-rethinking-resistance.html