INFORM October 2024

12 • inform October 2024, Vol. 35 (9)

The quest for new

antibiotics finds membrane lipids

Christiana Nunez

a new frontier,

Since they arrived on the market about four decades ago, carbapenems have been a go-to anti biotic for tough, life-threatening infections such as pneumonia or meningitis. When other drugs do not work, carbapenems often do. So, when the powerhouse of last resort began to fail against certain illnesses over the past couple of decades, it was one more worrying example of an ongoing global health threat, antimicrobial resistance.

Antimicrobial resistance is when bacteria or other pathogens stop responding to medicines. In 2019 alone, it contributed to nearly 5 mil lion deaths worldwide, directly causing more than 1 million of them. In the United States, treating six of the worst types of antimicrobial-re sistant infections cost an estimated $4.6 billion in 2017, according to a 2021 study. However, innovations in antibiotics have been few and far between, partly because of a lack of investment. A new avenue of research that targets membrane lipids offers hope for disabling some of the most dangerous bacteria. Researchers from the pharmaceutical company Roche have pinpointed a drug candidate that blocks the transport of a key glycolipid in carbapenem-resistant Acinetobacter baumannii (CRAB). Their paper, “A novel antibiotic class targeting the lipopolysaccharide transporter,” appeared in Nature in January (https://doi.org/10.1038/s41586-023-06799-7). “Antimicrobial resistance is often talked about as a silent pandemic. COVID-19 has brought this sharply into light, demonstrating the conse quences of a pandemic on the whole of society,” said Kenneth Bradley, global head of infectious disease discovery at Roche Pharma Research & Early Development, in an email interview. “The difference between anti microbial resistance and COVID-19 is that we have known about antimi crobial resistance for years.” THE RISE OF RESISTANT PATHOGENS Before the debut of penicillin in the 1940s and the other antibiotics that followed, an everyday wound could easily become deadly if it became infected. Patients who received penicillin early in its development included a woman who fell ill after a miscarriage and a man who had scratched himself working in his rose garden. In the era of commercial antibiotics, infectious diseases receded as a leading cause of death and life expectancies rose.

• Antimicrobial resistance is reducing the effectiveness of existing antibiotics, prompting a search for new strategies. • A drug candidate from the pharmaceutical company Roche blocks the transport of a key glycolipid in carbapenem-resistant Acinetobacter baumannii (CRAB). • Research, led by Uppsala University in Sweden, intends to disrupt the synthesis of membrane lipids in E. coli . • The studies demonstrate the potential of membrane lipids as an underexploited target in antibiotic treatments.