Antibiotic sensor directly binds drug in resistant bacteria
Vancomycin-resistant enterococci bacteria, or VRE, cause serious hospital-acquired infections, prompting scientists to search for new ways to target these hard-to-treat pathogens. VRE detect vancomycin through a transmembrane histidine kinase, called VanS, which phosphorylates the transcription factor VanR. Once phosphorylated, VanR triggers the production of enzymes that shield the bacterial cell wall from vancomycin’s effects. Ten genetic variants of this system exist, and disrupting it could restore vancomycin’s effectiveness. However, scientists do not understand how VanS senses vancomycin. Lina Maciunas, Photis Rotsides and a team at Drexel University College of Medicine tackled this question in their recent Journal of Biological Chemistry article.
The team developed an assay to study type-B VanS in nanodiscs, which mimic the cell membrane environment for purified membrane proteins. VanS performs three functions: autophosphorylation, transferring the phosphate group to VanR and dephosphorylating VanR. Testing these functions with vancomycin, the authors found increased autophosphorylation and slightly decreased dephosphorylation, consistent with the antibiotic activating the resistance system.
They then used a modified vancomycin photoaffinity probe and detected direct binding of the VanS sensor domain in the nanodisc, as assessed by mass spectrometry. Isothermal titration calorimetry confirmed that this interaction is specific for vancomycin since VanS did not bind a similar antibiotic.
Future work will explore how other VanS variants interact with vancomycin. Detailed insight into this interaction could guide inhibitor design to block antibiotic resistance in severe infections.
Enjoy reading ASBMB Today?
Become a member to receive the print edition four times a year and the digital edition monthly.
Learn moreGet the latest from ASBMB Today
Enter your email address, and we’ll send you a weekly email with recent articles, interviews and more.
Latest in Science
Science highlights or most popular articles

Mapping the placenta’s hormone network
Study uncovers how the placenta actively metabolizes not only glucocorticoids but also novel androgens and progesterones, reshaping our understanding of pregnancy and its complications.

Biochemists and molecular biologists sweep major 2025 honors
Recent Nobel, MacArthur and Kimberly Prize honorees highlight the power of biochemistry and molecular biology to drive discovery, including immune tolerance, vaccine design and metabolic disease, and to advance medicine and improve human health.

Spider-like proteins spin defenses to control immunity
Researchers from Utrecht University discovered two distinct binding modes of a spider-shaped immune inhibitor found in serum.

A biological camera: How AI is transforming retinal imaging
AI is helping clinicians see a more detailed view into the eye, allowing them to detect diabetic retinopathy earlier and expand access through tele-ophthalmology. These advances could help millions see a clearer future.

AI in the lab: The power of smarter questions
An assistant professor discusses AI's evolution from a buzzword to a trusted research partner. It helps streamline reviews, troubleshoot code, save time and spark ideas, but its success relies on combining AI with expertise and critical thinking.

Training AI to uncover novel antimicrobials
Antibiotic resistance kills millions, but César de la Fuente’s lab is fighting back. By pairing AI with human insight, researchers are uncovering hidden antimicrobial peptides across the tree of life with a 93% success rate against deadly pathogens.