Gram-negative bacteria's outer membrane was previously discovered to be made up of two non-protein components: lipids and carbohydrates, which together form an impermeable barrier.
Columbia University researchers have discovered how Gram-negative bacteria that cause drug-resistant pneumonia, bloodstream infections, and surgical site infections in hospitalized patients finish constructing a critical component of their outer membrane that protects them from immune system and antibiotic attacks.
The new findings suggest that developing newer medications to combat this potentially lethal bacteria, which is the source of innumerable infections in health-care settings around the world, should be accelerated.
The researchers were able to discover the structures of an O-antigen ligase (an enzyme that connects lipids and sugars) in two different functional configurations. How this lipopolysaccharide component comes together was the missing link, says Filippo Mancia, Ph.D., a study co-leader and professor.
After integrating genetic, biochemical, and molecular dynamics research, the scientists discovered how the enzyme places the lipids and sugars.
Mancia said, “ The lipopolysaccharide component of the outer membrane is critical to the survival of Gram-negative bacteria. “If you could block its assembly, then you would make the bacteria more sensitive to antibiotics and more vulnerable to the immune system.”
The construction of the membrane is a continuous process that begins when Gram-negative bacteria are first produced and continues when the membrane organically degrades and requires repair, according to the researchers. This means that there will be multiple opportunities to damage the membrane throughout the bacteria’s life cycle, not just at one point.
Researchers may be able to begin custom-designing medications that hinder the production of this protective membrane after identifying the structure of the enzyme that performs the final and important step in constructing Lipopolysaccharide barriers in drug-resistant bacteria.