Genentech Researchers Discover Novel Superbug-Targeting Treatment
The folding and insertion of integral β-barrel membrane proteins into the outer membrane of Gram-negative bacteria is required for viability and bacterial pathogenesis. And therefore, targeting such essential proteins or processes directly exposed to the environment could lead to the discovery of new agents to fight superbugs.
Now, Genentech researchers have found a chink in the armor of drug-resistant, gram-negative bacteria called the BamA enzyme, which is found in the bugs’ outer membrane. They believe they’ve found a way to attack this protein with an antibody—an approach that they say could pave the way for a new class of antibiotics to plug a treatment gap.
For their study, the team targeted BamA has it is found in all gram-negative bacteria, involved in a fundamental cell process, and exposed on the cell surface, eliminating the need to penetrate the cell.
They used a monoclonal antibody to block BamA function in E.coli, a gram-negative bacterium that has demonstrated drug resistance. As a result, this compromised the outer membrane, killing the bacteria.
Despite the initial goal being to identify a therapeutic antibody, the team did experience some limitations on moving it forward as a treatment. Throughout the process, the
team had to compete with lipopolysaccharide (LPS) in the outer membrane. It is particularly difficult to get the antibodies through this thick sugar layer, so they removed it during this study.“We used that antibody to ask some biological questions and learn about how Bam works,” said Steven Rutherford, a scientist at Genentech and corresponding author of the study. “It gives us an understanding of what it would take to inhabit this. It allows us to develop plans for the future to target this BamA machinery because it does present as a really useful and viable drug target.”
Even if Genentech aren’t able to develop an antibody-based antibiotic for gram-negative bacteria, the research will undoubtedly open up a number of doors for superbug-targeting treatments.
