CORRECTION! date is October 30, 2024 @ 13:30 (EDT) ----------------------------------------- Please Share .....
You are cordially invited to join us ..... "How vancomycin-resistant enterococci recognize vancomycin" Patrick Loll Department of Biochemistry & Molecular Biology, Drexel University College of Medicine October 30, 13:30(EDT) To register for virtual attendance: https://bnl.zoomgov.com/meeting/register/vJItf-utrT4tHjOXO25DBjC5kiYl6qlPwBQ Abstract: Vancomycin has historically served as an antibiotic of last resort, but its utility is threatened by the spread of resistance in many human pathogens, including vancomycin-resistant enterococci (VRE) Many different serotypes of VRE have been identified, with the two most clinically prevalent forms being types A and B. Each VRE type has acquired a suite of resistance genes, and in all cases expression of these genes is controlled by the VanRS two-component system. VanS is a membrane-bound sensor histidine kinase that detects vancomycin, leading to autophosphorylation; it then transduces this signal by phosphorylating VanR, thereby activating it as a transcription factor and stimulating transcription of the resistance genes. To date, little information has been available about how VanS senses the presence of vancomycin. We have now purified the VanS protein from type-B VRE and reconstituted it into nanodiscs to provide a membrane-like environment. Using a range of chemical biology and biophysical approaches, we show that this protein directly binds the antibiotic via its periplasmic domain, and that vancomycin binding leads to a marked stimulation of VanS’s autokinase activity. This represents the first time that a direct sensing mechanism has been confirmed for any VanS protein. The mechanistic details underlying vancomycin sensing are likely to reveal potential new approaches to antimicrobial drug therapy, for example the restoration of vancomycin sensitivity to VRE via blocking VanRS function. ######################################################################## To unsubscribe from the CCP4BB list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB&A=1 This message was issued to members of www.jiscmail.ac.uk/CCP4BB, a mailing list hosted by www.jiscmail.ac.uk, terms & conditions are available at https://www.jiscmail.ac.uk/policyandsecurity/
