Resistant bacteria meet their match with custom antibiotics

By Levi Gadye / Mon Oct 26, 2020

Paul Gunning (Cell Image Library)

A scanning electron micrograph image of methicillin resistant staphylococcus aureus (MRSA) bacteria.

Bacterial resistance is a growing problem. About 2.8 million people are infected by resistant bacteria or fungi each year, leading to 35,000 deaths. Scientists at the UCSF School of Pharmacy have shown that engineering small molecular changes into some antibiotics can restore their effectiveness in stopping the growth of drug-resistant bacteria.

Ian Seiple, PhD, faculty member in the School’s Department of Pharmaceutical Chemistry and the UCSF Cardiovascular Research Institute, systematically modified a group of antibiotics to skirt the defenses of drug-resistant bacteria.

Seiple’s revamped antibiotics beat back these bacteria. He then worked with James Fraser, PhD, faculty member in the Department of Bioengineering and Therapeutic Sciences, to understand how these modifications work.

He provides an overview of the research, which was published September 23 in Nature, in the video below.

Ian Seiple, PhD, explains how he improved antibiotics to make them effective against resistant bacteria.

Transcript

As recently as 100 years ago every minor injury or routine surgery came with significant risk of infection or even death. The discovery of antibiotics changed that, and they are now essential components of modern medicine. But many bacteria are becoming resistant to these drugs, and we aren’t discovering enough new ones to keep up. My laboratory is building new molecules from simple chemical building blocks, much like Legos, to revitalize antibiotics that haven’t yet reached their full potential. We recently used this approach to improve antibiotics known as streptogramins, which some bacteria are able to deactivate. We built new streptogramins that have a molecular bump that prevents deactivation, overcoming resistance. Working with the Fraser Lab, we are visualizing how these new streptogramins work and are now applying insights from this research to improve other antibiotics. It’s our hope that these efforts will keep medicine one or two steps ahead of deadly, resistant bacteria for decades to come.

Customizable Synthetic Antibiotic Outmaneuvers Resistant Bacteria (UCSF News)

Synthetic group A streptogramin antibiotics that overcome Vat resistance (Nature)