Journal article
The VanS sensor histidine kinase from type-B vancomycin-resistant enterococci recognizes vancomycin directly
The Journal of biological chemistry, v 301(6), 110276
22 May 2025
PMID: 40412528
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Vancomycin-resistant enterococci (VRE) are high-priority targets for new therapeutic development. In VRE, expression of the resistance phenotype is controlled by the VanRS two-component system, which senses the presence of the antibiotic and responds by initiating transcription of resistance genes. VanS is a transmembrane sensor histidine kinase that is known to detect the antibiotic and then transduce this signal to the VanR transcription factor; however, fundamental questions remain about how exactly VanS senses vancomycin. Here, we focus on a purified VanRS system from one of the most clinically prevalent forms of VRE, type B. We show that in a native-like membrane environment, vancomycin strongly stimulates the autokinase activity of type-B VanS. We additionally demonstrate that this effect is mediated by a direct physical interaction between the antibiotic and the VanS periplasmic domain. This represents the first time that a direct sensing mechanism has been confirmed for any VanS protein from a human pathogen.
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Details
- Title
- The VanS sensor histidine kinase from type-B vancomycin-resistant enterococci recognizes vancomycin directly
- Creators
- Lina J Maciunas - Drexel UniversityPhotis Rotsides - Drexel UniversityElizabeth J D'LauroSamantha Brady - Drexel UniversityJoris Beld - Drexel UniversityPatrick J Loll - Drexel University
- Publication Details
- The Journal of biological chemistry, v 301(6), 110276
- Publisher
- Elsevier
- Number of pages
- 14
- Grant note
- NIH: R01AI148679, F31AI136385
Funding for this work was provided by NIH grants R01AI148679 (P. J. L.) and F31AI136385 (L. J. M.) . The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology; Microbiology and Immunology
- Web of Science ID
- WOS:001513611800003
- Scopus ID
- 2-s2.0-105008088033
- Other Identifier
- 991022054115104721
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- Web of Science research areas
- Biochemistry & Molecular Biology