A Weakness in Bacterial Defenses?

Scientists at the University of East Anglia have figured out a chink in bacterial armor, potentially paving the way for novel drug development at a time when antibiotic resistance is becoming a critical global health problem.

Published June 26, 2014

A Weakness in Bacterial Defenses?

According to the World Health Organization, "antibiotic resistance—when bacteria change so antibiotics no longer work in people who need them to treat infections—is now a major threat to public health." This BBC feature explains the issue in beautifully/disturbingly illustrated detail. In short, disease-causing microbes are evolving molecular countermeasures to drugs at a far faster rate than we're discovering new interventions.

However, a group of scientists at the University of East Anglia recently scored a point for Team Humans by mapping the structure of a protein used by a large class of bacteria to construct a defensive outer membrane. Gram-negative bacteria cause a swath of illnesses including pneumonia, salmonella, meningitis, and bloodstream and wound infections. They're also exceptionally difficult to kill because the outer membrane provides protection from immune cells and antibiotics.

A key component of this natural armor is a molecule called lipopolysaccharide, which gets delivered to its place in the protective layer by transporter proteins called LptD and LptE. Researchers at UEA collaborated with scientists at the Diamond synchrotron to blast these transporters with super high-powered x-rays, the diffraction pattern of which reveals the atomic structure of the protein.

When it comes to proteins, form and function go firmly hand in hand. Using the atomic blueprint as a guide, the team was able to model the function of the LptDE complex.

"We have identified the path and gate used by the bacteria to transport the barrier building blocks to the outer surface. Importantly, we have demonstrated that the bacteria would die if the gate is locked," says lead researcher Prof.Changjiang Dong in this press release. "If the bacteria do not have the outer membrane, they cannot withstand environmental changes. It also makes it easier for the human immune system to kill them."

Now that the structure and mechanisms of the bacterial defenses are understood, it may be possible to develop drugs to interfere with their function. "The really exciting thing about this research is that new drugs will specifically target the protective barrier around the bacteria, rather than the bacteria itself," says study author Haohoa Dong. "Because new drugs will not need to enter the bacteria itself, we hope that the bacteria will not be able to develop drug resistance in future."

It's too soon to say, but at least it's a start.

 

 


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