A team of researchers from the University of East Anglia has discovered a possible new drug target in a class of bacteria which could pave way for a new generation of antibiotics that could help fight the ever-growing problem of antibiotic resistance. The study has been published in Nature.
The pressure is on for scientists around the world to develop new ways to combat bacterial infections given the alarmingly widespread nature of antibiotic resistance. The problem was highlighted in a recent WHO report which detailed antimicrobial resistance levels worldwide and called for a concerted effort to tackle the issue which has been called a “global health security threat.” There is therefore a dire need for scientists to come up with novel ways to tackle microbes that are also tricky to evolve resistance to, and UEA researchers believe they may have done just that.
The team investigated a class of bacteria known as Gram-negative bacteria. Bacterial species within this class cause a variety of infections such as pneumonia, meningitis, bloodstream infections and wound infections. These bacteria possess a unique outer membrane which is particularly difficult for drugs to permeate, providing inherent resistance to numerous antibiotics.
A major component of this outer membrane is a molecule called lipopolysaccharide (LPS) which helps to stabilize the lipid membrane and also plays key roles in protecting the bacteria from toxic compounds. Although scientists knew which bacterial proteins were involved in the transport of LPS to the outer membrane, the mechanism was poorly understood until now.
The researchers discovered that a complex of two transport proteins, LptD and LptE, form a “barrel and plug” structure that helps to pull LPS molecules from the inner membrane to the outer membrane where a portion of the LPS can then be inserted into the outer leaflet.
“We have identified the path and gate used by the bacteria to transport the barrier building blocks to the outer surface,” said lead researcher Prof Changjiang Dong in a news-release. “Importantly, we have demonstrated that the bacteria would die if the gate is locked.”
Dong stresses the significance of these findings given that so many antibiotics are becoming useless. “This research provides the platform for urgently-needed new generation drugs,” he added.
Although this research is certainly in its infancy, the scientists believe that if they can develop compounds that target this system then they may have a valid way to combat multi-drug-resistant bacteria. Furthermore, they think that these drugs would be particularly tricky for bacteria to evolve resistance to since they will not need to actually enter the bacteria.