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
When things get SAPpy: Novel insights into complement
Researchers have defined interactions between an innate immune protein and two of its known binding partners. They identified potential areas of crosstalk between the two binding interactions.
Glutathione pathway implicated in rare disease
Researchers found that glutathione metabolism plays a central role in the pathogenesis of rare disease methylmalonic aciduria using a novel multiomics approach.
A p-value for proteins
Kyoto University researchers developed UniScore, a new tool that uses a target-decoy method to filter false positives in proteomic searches, helping scientists set thresholds and improve reliability when analyzing complex protein data.
Novel way to uncover tumor microenvironment proteomics
Researchers at the Weizmann Institute of Science developed a novel single-cell approach that facilitates the study of proteins surrounding lung cancer cells.
Sizing up cells: How stem cells know when to divide
Stanford University researchers find that stem cells control their size early in cell division across living multicellular systems.
When oncogenes collide in brain development
Researchers at University Medical Center Hamburg, found that elevated oncoprotein levels within the Wnt pathway can disrupt the brain cell extracellular matrix, suggesting a new role for LIN28A in brain development.