Mechanism behind bacterias antibiotic resistance identified

Scientists have taken a step forward in the battle against bacteria by deciphering the molecular mechanism behind selective antimicrobial activity for a prototypical class of synthetic compounds

Washington, Sep 21 : Scientists have taken a step forward in the battle against bacteria by deciphering the molecular mechanism behind selective antimicrobial activity for a prototypical class of synthetic compounds

The University of Illinois and the University of Massachusetts researchers say that the findings could shorten the road to new and more potent antibiotics.

The rapid development of bacterial resistance to conventional antibiotics, such as penicillin or vancomycin, has become a major public health concern. Because resistant strains of bacteria can arise faster than drug companies can create antibiotics, understanding how these molecules function could help companies narrow their focus on potential antibiotics and bring them to market sooner.

The prototypical class of synthetic compounds, which mimic antimicrobial peptides found in biological immune systems, "function as molecular 'hole punchers,' punching holes in the membranes of bacteria," said Gerard Wong, a professor of materials science and engineering, physics, and bioengineering at the U. of I., and a corresponding author of the paper.

"It's a little like shooting them with a hail of nanometer-sized bullets - the perforated membranes leak and the bacteria consequently die," he added.

The researchers also found why some compounds punch holes only in bacteria, while others kill everything within reach, including human cells.

"We can use this as a kind of Rosetta stone to decipher the mechanisms of much more complicated antimicrobial molecules. If we can understand the design rules of how these molecules work, then we can assemble an arsenal of killer molecules with small variations, and no longer worry about antimicrobial resistance," Wong said.

For the study, the researchers first synthesized a prototypical class of antimicrobial compounds, and then used synchrotron small-angle X-ray scattering to study the structures made by the synthetic compounds and cell membranes.

Composed of variously shaped lipids, including some that look like traffic cones, the cell membrane regulates the passage of materials in and out of the cell. In the presence of the researchers' antimicrobial molecules, the cone-shaped lipids gather together and curl into barrel-shaped openings that puncture the membrane, and lead to cell death.

Wong said that the efficacy of an antimicrobial molecule depends on both the concentration of cone-shaped lipids in the cell membrane, and on the shape of the antimicrobial molecule.

"By understanding how these molecules kill bacteria, and how we can prevent them from harming human cells, we can provide a more direct and rational route for the design of future antibiotics," Wong said.

The study is published in the Journal of the American Chemical Society.

ANI