Secret to Success of Drug-Resistant Bacteria

Scientists have identified how Gram-negative bacteria— which cause drug-resistant pneumonia, bloodstream infections, and surgical site infections in hospitalized patients– complete building a crucial element of their outer membrane that guards these pathogens against attacks by the immune system and antibiotics.

The brand-new findings could speed up the advancement of novel medications to offset these potentially deadly bacteria, the source of numerous infections in health care settings worldwide.

The research study was released online on April 6 in Nature.

“Previously, we knew that Gram-negative bacteria build their external membrane with two main, non-protein components– lipids and also sugars– which collectively create an impermeable barrier. The missing connection was how this lipopolysaccharide component comes together,” claims Filippo Mancia, Ph.D., a co-leader of the research study and professor of physiology and cellular biophysics at Columbia University Vagelos College of Physicians and Surgeons.

Using innovative single-particle cryo-electron microscopy, Mancia and colleagues could determine the enzyme structures that connect the lipids and sugars (called an O-antigen ligase) in 2 distinct functional configurations. Combining genetic, biochemical, and molecular dynamics experiments, the team learned exactly how the enzyme positions the lipids and sugars so that they can mix to form the protective membrane.

The Gram-negative bacteria

The lipopolysaccharide element of the outer membrane layer is critical to the survival of Gram-negative bacteria. “If you can obstruct its assembly, after that, you would certainly make the bacteria much more sensitive to antibiotics and even more unprotected to the immune system,” Mancia claims.

Construction of this membrane is an ongoing process, beginning when Gram-negative bacteria are first created and going on as the membrane layer naturally weakens and calls for repair. “This suggests that we would have numerous chances to disrupt the membrane layer, not just at one stage of the bacteria’s life cycle,” Mancia states.

After disclosing the enzyme’s structure that executes the last and essential step in constructing lipopolysaccharide barriers in drug-resistant bacteria, scientists might start to custom-design medications that prevent the biosynthesis of this protective membrane layer.

Read the original article on Science Daily.

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