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  • Author(s):
    Chinedu Madukoma, Shusuke Tomoshige, Choonkeun Kim, Elan Lastochkin, William C. Boggess, Jed Fisher, Joshua Shrout, Shahriar Mobashery
    Abstract:

    The interplay between the activities of lytic transglycosylases (LTs) and penicillin-binding proteins (PBPs) is critical for the health of the bacterial cell wall. Bulgecin A (a natural-product inhibitor of LTs) potentiates the activity of β-lactam antibiotics (inhibitors of PBPs), underscoring this intimate mechanistic interdependence. Bulgecin A in the presence of an appropriate β-lactam causes bulge deformation due to the formation of aberrant peptidoglycan at the division site of the bact…

    Date Published:
    2019-01
    Record Visibility:
    Public
  • Author(s):
    Trung T. Nguyen, Jeffrey Jones, Walter Wolter, Rocio Perez, Valerie Schroeder, Matthew Champion, Dusan Hesek, Mijoon Lee, Mark Suckow, Shahriar Mobashery, Mayland Chang
    Abstract:

    Diabetic foot ulcers are characterized by hypoxia. For many patients, hyperbaric oxygen (HBO) therapy is the last recourse for saving the limb from amputation, for which the molecular basis is not understood. We previously identified the active form of matrix metalloproteinase-9 (MMP-9) as responsible for diabetic foot ulcer’s recalcitrance to healing. Transcription of mmp-9 to the inactive zymogen is upregulated during hypoxia. Activation of the zymogen is promoted by proteases and react…

    Record Visibility:
    Public
  • Author(s):
    Jeshina Janardhanan, Renee Bouley, Sisth Martinez-Caballero, Zhihong Peng, Mayte Batuecas-Mordillo, Jayda E. Meisel, Derong Ding, Valerie Schroder, William Wolter, Juan Hermoso, Shahriar Mobashery, Mayland Chang
    Abstract:

    The quinazolinones are a new class of antibacterials with in vivo efficacy against methicillin-resistant Staphylococcus aureus (MRSA). The quinazolinones target cell wall biosynthesis and have a unique mechanism of action by binding to the allosteric site of penicillin-binding protein 2a (PBP 2a). We investigated the potential for synergism of a lead quinazolinone with several antibiotics of different classes using checkerboard and time-kill assays. The quinazolinone synergized with β-lactam …

    Date Published:
    2019-03
    Record Visibility:
    Public
  • Author(s):
    Trung T. Nguyen, Derong Ding, William R. Wolter, Matthew M. Champion, Dusan Hesek, Mijoon Lee, Rocio L. Pérez, Valerie A. Schroeder, Mark A. Suckow, Shahriar Mobashery, Mayland Chang
    Abstract:

    Chronic wounds are a complication of diabetes. Treatment for diabetic foot ulcers is complex with little clinical recourse, resulting in 108,000 lower-limb amputations annually in the United States alone. Matrix metalloproteinases (MMPs) play important roles in the pathology and in the repair of chronic wounds. We previously identified active MMP-8 and MMP-9 in wounds of diabetic mice and determined that MMP-8 accelerates wound repair, while MMP-9 is the culprit for the diabetic wound being r…

    Date Published:
    2018
    Record Visibility:
    Public