Even ciprofloxacin, an antibiotic used to treat a variety of bacterial infections including inhaled anthrax, is no match for AcrB. In this image, the green-colored drug is firmly ensnared in the protein’s cavity.
In the race to stay one step ahead of drug-resistant bacteria, scientists from Lawrence Berkeley National Laboratory and the University of California at Berkeley obtained high-resolution images of a protein complex found in bacteria that repels a wide range of antibiotics.
The images, which appear in the May 9 issue of Science, offer new insight into how bacteria survive attacks from different antibiotics, a growing health problem called multidrug resistance. As the team learned, these robust defenses are rooted in the protein complex’s remarkable ability to capture and pump out a spectrum of structurally diverse compounds. The research may inform the development of antibiotics that either evade or inhibit these pumps, allowing drugs to slip inside bacteria cells and kill them.
The team focused their inquiry on AcrB, a protein that resides in the inner membrane of Escherichia coli cells. It works in unison with two other proteins to rid the bacteria of toxins. Based on earlier research, they knew AcrB boasts a large cavity capable of binding with a vast range of antibiotics and other molecules. But precisely how this cavity accommodates so many shapes and sizes remained unclear. To witness this trickery, the team crystallized the protein in the presence of four molecules — an antibiotic, a dye, a disinfectant, and a DNA binding molecule — and then turned to Berkeley Lab’s Advanced Light Source (ALS). There, they exposed the crystals to extremely bright x-rays that reveal the protein’s molecular structure, including how the four molecules bind to the cavity.
Dan Krotz | EurekAlert!
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