Browsing by Author "Chopra, Jay"

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    Amino acid divergence in the ligand-binding pocket of Vibrio LuxR/HapR proteins determines the efficacy of thiophenesulfonamide inhibitors
    (Wiley, 2021) Newman, Jane D.; Chopra, Jay; Shah, Priyanka; Shi, Eda; McFadden, Molly E.; Horness, Rachel E.; Brown, Laura C.; van Kessel, Julia C.; Medicine, School of Medicine
    The quorum sensing signaling systems in Vibrio bacteria converge to control levels of the master transcription factors LuxR/HapR, a family of highly conserved proteins that regulate gene expression for bacterial behaviors. A compound library screen identified 2-thiophenesulfonamide compounds that specifically inhibit Vibrio campbellii LuxR but do not affect cell growth. We synthesized a panel of 50 thiophenesulfonamide compounds to examine the structure-activity relationship effects on Vibrio quorum sensing. The most potent molecule identified, PTSP (3-phenyl-1-(thiophen-2-ylsulfonyl)-1H-pyrazole), inhibits quorum sensing in multiple strains of Vibrio vulnificus, Vibrio parahaemolyticus, and V. campbellii at nanomolar concentrations. However, thiophenesulfonamide inhibition efficacy varies significantly among Vibrio species: PTSP is most inhibitory against V. vulnificus SmcR, but V. cholerae HapR is completely resistant to all thiophenesulfonamides tested. Reverse genetics experiments show that PTSP efficacy is dictated by amino acid sequence in the putative ligand binding pocket: F75Y and C170F SmcR substitutions are each sufficient to eliminate PTSP inhibition. Further, in silico modeling distinguished the most potent thiophenesulfonamides from less effective derivatives. Our results revealed the previously unknown differences in LuxR/HapR proteins that control quorum sensing in Vibrio species and underscore the potential for developing thiophenesulfonamides as specific quorum sensing-directed treatments for Vibrio infections.
  • Thumbnail Image
    Item
    Comparing reactivation and retreatment of three doses of bevacizumab in type 1 retinopathy of prematurity
    (Elsevier, 2024-04) Chopra, Jay; Haider, Kathryn M.; Boente, Charline S.; Ophthalmology, School of Medicine
    Purpose To determine timing and rates of reactivation and retreatment of type 1 retinopathy of prematurity (ROP) after treatment with either 0.125 mg, 0.250 mg, or 0.500 mg of intravitreal bevacizumab (IVB). Methods Retrospective data, including demographic information, past medical history, and ROP characteristics were analyzed for babies with type 1 ROP treated with IVB at Riley Hospital for Children for the period 2014-2021. Results A total of 84 patients met inclusion criteria: 29 patients received 0.125 mg of IVB; 39, 0.250 mg; and 16, 0.500 mg. Of the 84, 67 (80%) had additional laser treatment because of late reactivation (n = 52) or persistent avascular retina (PAR) (n = 15). Subsequent laser treatment was more common with lower doses: 0.125 mg (n = 27 [93%]); 0.250 mg (n = 31 [80%]); 0.500 mg (n = 9 [57%]) (P = 0.012). There was no difference between groups with regard to reason for subsequent laser treatment (reactivation vs PAR). The 0.125 mg group required retreatment because of reactivation 3.8 weeks sooner than the other dosing groups (P = 0.047). Conclusions The outcomes comparing three doses of IVB for severe ROP showed a difference in the timing of secondary treatment, with the lower dosing group requiring laser for reactivation earlier.