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Bayesian Modeling and Intrabacterial Drug Metabolism Applied to Drug-Resistant Staphylococcus aureus.
Patel, Jimmy S; Norambuena, Javiera; Al-Tameemi, Hassan; Ahn, Yong-Mo; Perryman, Alexander L; Wang, Xin; Daher, Samer S; Occi, James; Russo, Riccardo; Park, Steven; Zimmerman, Matthew; Ho, Hsin-Pin; Perlin, David S; Dartois, Véronique; Ekins, Sean; Kumar, Pradeep; Connell, Nancy; Boyd, Jeffrey M; Freundlich, Joel S.
Afiliación
  • Patel JS; Department of Pharmacology, Physiology, and Neuroscience, Rutgers University - New Jersey Medical School, 185 South Orange Ave, Newark, New Jersey 07103, United States.
  • Norambuena J; Department of Biochemistry and Microbiology, Rutgers, The State University of New Jersey, New Brunswick, New Jersey 08901, United States.
  • Al-Tameemi H; Department of Biochemistry and Microbiology, Rutgers, The State University of New Jersey, New Brunswick, New Jersey 08901, United States.
  • Ahn YM; Department of Pharmacology, Physiology, and Neuroscience, Rutgers University - New Jersey Medical School, 185 South Orange Ave, Newark, New Jersey 07103, United States.
  • Perryman AL; Department of Pharmacology, Physiology, and Neuroscience, Rutgers University - New Jersey Medical School, 185 South Orange Ave, Newark, New Jersey 07103, United States.
  • Wang X; Department of Pharmacology, Physiology, and Neuroscience, Rutgers University - New Jersey Medical School, 185 South Orange Ave, Newark, New Jersey 07103, United States.
  • Daher SS; Department of Pharmacology, Physiology, and Neuroscience, Rutgers University - New Jersey Medical School, 185 South Orange Ave, Newark, New Jersey 07103, United States.
  • Occi J; Department of Medicine, Center for Emerging and Re-emerging Pathogens, Rutgers University - New Jersey Medical School, Newark, New Jersey 07103, United States.
  • Russo R; Department of Medicine, Center for Emerging and Re-emerging Pathogens, Rutgers University - New Jersey Medical School, Newark, New Jersey 07103, United States.
  • Park S; Public Health Research Institute, Rutgers University - New Jersey Medical School, 225 Warren St, Newark, New Jersey 07103, United States.
  • Zimmerman M; Public Health Research Institute, Rutgers University - New Jersey Medical School, 225 Warren St, Newark, New Jersey 07103, United States.
  • Ho HP; Public Health Research Institute, Rutgers University - New Jersey Medical School, 225 Warren St, Newark, New Jersey 07103, United States.
  • Perlin DS; Public Health Research Institute, Rutgers University - New Jersey Medical School, 225 Warren St, Newark, New Jersey 07103, United States.
  • Dartois V; Public Health Research Institute, Rutgers University - New Jersey Medical School, 225 Warren St, Newark, New Jersey 07103, United States.
  • Ekins S; Collaborations in Chemistry, 5616 Hilltop Needmore Road, Fuquay-Varina, North Carolina 27526, United States.
  • Kumar P; Department of Medicine, Center for Emerging and Re-emerging Pathogens, Rutgers University - New Jersey Medical School, Newark, New Jersey 07103, United States.
  • Connell N; Department of Medicine, Center for Emerging and Re-emerging Pathogens, Rutgers University - New Jersey Medical School, Newark, New Jersey 07103, United States.
  • Boyd JM; Department of Biochemistry and Microbiology, Rutgers, The State University of New Jersey, New Brunswick, New Jersey 08901, United States.
  • Freundlich JS; Department of Pharmacology, Physiology, and Neuroscience, Rutgers University - New Jersey Medical School, 185 South Orange Ave, Newark, New Jersey 07103, United States.
ACS Infect Dis ; 7(8): 2508-2521, 2021 08 13.
Article en En | MEDLINE | ID: mdl-34342426
We present the application of Bayesian modeling to identify chemical tools and/or drug discovery entities pertinent to drug-resistant Staphylococcus aureus infections. The quinoline JSF-3151 was predicted by modeling and then empirically demonstrated to be active against in vitro cultured clinical methicillin- and vancomycin-resistant strains while also exhibiting efficacy in a mouse peritonitis model of methicillin-resistant S. aureus infection. We highlight the utility of an intrabacterial drug metabolism (IBDM) approach to probe the mechanism by which JSF-3151 is transformed within the bacteria. We also identify and then validate two mechanisms of resistance in S. aureus: one mechanism involves increased expression of a lipocalin protein, and the other arises from the loss of function of an azoreductase. The computational and experimental approaches, discovery of an antibacterial agent, and elucidated resistance mechanisms collectively hold promise to advance our understanding of therapeutic regimens for drug-resistant S. aureus.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Infecciones Estafilocócicas / Preparaciones Farmacéuticas / Staphylococcus aureus Resistente a Meticilina Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: ACS Infect Dis Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Infecciones Estafilocócicas / Preparaciones Farmacéuticas / Staphylococcus aureus Resistente a Meticilina Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: ACS Infect Dis Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos